CRPS is a common disorder not completely understood, with no data available regarding the incidence of paediatric CRPS  because the diagnosis is uncertain and underestimated. Clinical evaluation, including a neurologic exam, combined with a thorough history collection is mandatory  to rule out other possible reasons for chronic pain, such as orthopaedic, neurological and rheumatologic conditions . Early diagnosis is as important as or more than treatment; in fact, a longer disease course and sequelae  are associated with late identification. Unfortunately, no specific diagnostic tools have been developed for children and adolescents, so the adult criteria are used . Orthopaedists have a key role in the recognition of the disease due to very little evidence, no common consensus among the physicians, and a lack of guidelines . As reported by Berde and Lebel , often the choice of treatment may vary according to the experience and resources of the clinician. Several treatments have been described , including acupuncture, transcranial magnetic stimulation, and invasive procedures, but the efficacy has been proven for the combination of physical and cognitive behavioural therapy and some pharmacological treatments only. The most established treatment is a programme of physical rehabilitation and cognitive behavioural therapy . The goal is to restore normal function, increase the joint motion range, load tolerance and strength, and concurrently assist the child in accepting and managing the pain . Different protocols were illustrated in selected studies, highlighting the absence of a standard treatment protocol. Sherry and colleagues  suggested aerobic training and progressive resistive exercises, in addition to hydrotherapy, desensitization with towel rubbing, hand massage, textured fabric rubs, and contrast baths (2 °C and 38 °C). During the patient’s hospitalization, 5–6 hours of daily exercise therapy and 45 minutes to 3 hours of home exercise programmes (HEPs) were performed. In the Logan et al. trial , the patients underwent open-chain and closed-chain activities and an individualized HEP, and each child’s functional goals, such as playing a specific sport, were incorporated into the physical schedule. In addition, this multidisciplinary rehabilitation approach addresses the entire pain experience, incorporating desensitization, exposure to feared activities, skills for coping with pain, and changes to social responses to pain. Lee et al.  designed a protocol including transcutaneous electrical nerve stimulation, progressive weight bearing, tactile desensitization, massage, contrast baths and an HEP. Six weekly sessions of individual CBT incorporating pain management strategies, including relaxation training, deep breathing exercises, biofeedback, and guided imagery, were also included. Patient compliance, nurse care and parent treatment programmes  are mandatory to promote successful remission from pain and restoration of functional ability. Despite a rigorous rehabilitation programme, Sherry et al. described their patients as a motivated and eager to please sample . Lee et al.  recorded compliance varying between 78 and 82%. No adverse events were recorded in the three studies, but the remission rate varied between 79% and 100% [10–12]. Several authors have investigated the role of PT + CBT in paediatric CRPS type 1, especially the brain and neurological changes and treatment action on the central nervous system. Frot et al. found evidence of emotional integration of pain in CRPS patients . Lebel et al.  concluded that some changes in the brain persist, especially in the amygdala and basal ganglia, even after symptomatic recovery . Diers et al.  demonstrated that behavioural extinction training reduces the emotional involvement in processing painful stimuli and induces a shift to a more sensory-discriminative way of pain processing post-treatment. Kregel et al.  emphasize that conservative treatments for patients with chronic musculoskeletal pain may induce both functional and morphological changes in predominantly prefrontal brain regions. For these reasons, non-invasive treatments are often recommended, even in recurrent forms [2, 4]. On the other hand, the literature presents evidence of good outcomes after intravenous infusion of drugs and regional nerve blockades. Three pharmacological trials were selected in the study, and different molecules were investigated. Petje et al.  assessed the outcome of iloprost intravenous infusion, an analogue of prostacyclin, which induces transitory complete sympathicolysis and avoids the anxiety associated with a lumbar sympathetic blockade. Despite the good rate of response, relevant adverse reactions such as headache, flushing, vomiting, and a decrease in systolic blood pressure were recorded in all cohorts; consequently, the same authors do not suggest iloprost as primary therapy. Other drugs proposed for treating neuropathic pain were gabapentin and amitriptyline. The first avoids the release of neurotransmitters acting on voltage-gated calcium channels , and the latter e neuropathic reinforces the serotonin transporter . Brown et al. compared the two molecules in a refractory PT + CBT schedule. The series revealed that both drugs are effective in reducing pain scores and improving sleep, without significant differences. However, ventricular conduction abnormalities were noted in the gabapentin group, while amitriptyline was linked to QT prolongation, torsade de pointes and sudden cardiac death. For these reasons, the use of both drugs in selected patients and with proper monitoring may be considered. Several invasive options have been proposed, including the use of continuous regional anaesthesia with epidural or peripheral catheters, which demonstrate a reduction in pain score and improvement in function score at short- and long-term follow-up. On the other hand, in the Donado et al. series , 39% of the sample did not clinically improve the pain symptoms, and 43% had no functional advantages. Nevertheless, the authors suggested the treatment in addition to an active PT + CBT protocol. All the studies included in the systematic review emphasized the utility of PT + CBT, even when additional approaches were undertaken. The comparison of management with versus without rehabilitation was considered ethically unacceptable ; however, the outcome can be not related to a single treatment, and the results have been influenced by conservative treatment even in pharmacologic protocol studies. Future research directions should focus on the identification of disease onset mechanisms and the development of more defined, proper and easy-to-use diagnostic tools. The design of high-quality, prospective, large-cohort, long-term follow-up studies is strongly encouraged, as is design of a specific assessment score. The heterogeneity of the scores utilized in the objective clinical assessment of the patients, the absence of standard protocols, and the lack of randomized, blinded prospective trials are the main limits in the comparison of study results.