Calcium ions (Ca²⁺) are critical secondary messengers in our cells, shuttling messages from outside cells to within. Ca²⁺ signaling depends on transport proteins to move ions across membranes. Store-operated channels (SOCs) are one particularly important class of transporters for Ca²⁺ signaling. SOCs allow Ca²⁺ signaling to continue by refilling critical Ca²⁺ stores in a process called store-operated Ca²⁺ entry (SOCE). Our cardiovascular system is particularly dependent on Ca²⁺ signaling, even in non-excitable (i.g., non-muscle) cells like vascular endothelial cells. Growing evidence suggests that malfunctions in SOCs and the SOCE process contribute to many cardiovascular diseases. But the exact roles of SOCs and SOCE are not fully understood. A recent review examined the current literature on SOC function in the vasculature and what is currently known about SOCs' role in cardiovascular disease. Current evidence suggests that therapeutics aimed at SOCE are a promising treatment target, but the current pharmacological tools used to determine the contribution of SOCE constituents in cardiovascular disease lack specificity. Therefore, further research is needed to determine the precise roles of SOCs and other contributors to SOCE in cardiovascular disease.