Calcium is a crucial mediator of cell signaling in skeletal muscles for basic cellular functions and specific functions, including contraction, fiber-type differentiation and energy production. The sarcoplasmic reticulum (SR) is an organelle that provides a large supply of intracellular Ca²⁺ in myofibers. Upon excitation, it releases Ca²⁺ into the cytosol, inducing contraction of myofibrils. During relaxation, it takes up cytosolic Ca²⁺ to terminate the contraction. During exercise, Ca²⁺ is cycled between the cytosol and the SR through a system by which the Ca²⁺ pool in the SR is restored by uptake of extracellular Ca²⁺ via a specific channel on the plasma membrane. This channel is called the store-operated Ca²⁺ channel or the Ca²⁺ release-activated Ca²⁺ channel. It is activated by depletion of the Ca²⁺ store in the SR by coordination of two main molecules: stromal interaction molecule 1 (STIM1) and calcium release-activated calcium channel protein 1 (ORAI1). Recently, myopathies with a dominant mutation in these genes have been reported and the pathogenic mechanism of such diseases have been proposed. This review overviews the calcium signaling in skeletal muscles and role of store-operated Ca²⁺ entry in calcium homeostasis. Finally, we discuss the phenotypes and the pathomechanism of myopathies caused by mutations in the STIM1 and ORAI1 genes.