The candidate phyla radiation (CPR) is a diverse group of small bacteria that are likely obligate intracellular symbionts. Despite recent research attention, little is known about CPR bacteria in wastewater treatment systems. To close this gap, researchers recently examined the CPR community over an 11-year period in activated sludge systems. Approximately 9% of the AS bacterial metagenome-assembled genomes were affiliated with CPR, and CPR bacteria were consistently abundant with a relative abundance of up to 7.5%. There were striking fluctuations in the CPR community, and CPR members had limited metabolic and biosynthetic capabilities, suggesting that CPR dynamics are directly determined by the available hosts. Similarity-based network analysis confirmed a broad range of bacterial hosts for CPR members. Even though these wastewater treatment plants handle municipal water, the CPR proteome in this study was more like environmental CPR proteomes than human-associated ones. The CPR genomes had many oxygen stress resistance genes as well as genes for carbon cycling and horizontal gene transfer. Overall, the results highlight the importance of specific host interactions among CPR lineages in activated sludge and that, despite lacking key metabolic pathways, these tiny bacteria may be significantly involved in biogeochemical cycling.