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Calcium signaling in vascular endothelial cells (ECs) and smooth muscle cells (VSMCs) is essential for the regulation of vascular tone. However, the changes to intracellular Ca 2+ concentrations are often influenced by sex differences. Furthermore, a large body of evidence shows that sex hormone imbalance leads to dysregulation of Ca 2+ signaling and this is a key factor in the pathogenesis of cardiovascular diseases. In this review, the effects of estrogens and androgens on vascular calcium-handling proteins are discussed, with emphasis on the associated genomic or nongenomic molecular mechanisms. The experimental models from which data were collected were also considered. The review highlights 1 ) in female ECs, transient receptor potential vanilloid 4 (TRPV4) and mitochondrial Ca 2+ uniporter (MCU) enhance Ca 2+ -dependent nitric oxide (NO) generation. In males, only transient receptor potential canonical 3 (TRPC3) plays a fundamental role in this effect. 2 ) Female VSMCs have lower cytosolic Ca 2+ levels than males due to differences in the activity and expression of stromal interaction molecule 1 (STIM1), calcium release-activated calcium modulator 1 (Orai1), calcium voltage-gated channel subunit-α 1C (Ca V 1.2), Na + -K + -2Cl - symporter (NKCC1), and the Na + /K + -ATPase. 3 ) When compared with androgens, the influence of estrogens on Ca 2+ homeostasis, vascular tone, and incidence of vascular disease is better documented. 4 ) Many studies use supraphysiological concentrations of sex hormones, which may limit the physiological relevance of outcomes. 5 ) Sex-dependent differences in Ca 2+ signaling mean both sexes ought to be included in experimental design.