Calcium is a universal messenger regulating many physiological functions, including the ability of the cell to undergo orderly self-destruction upon completion of its function, called apoptosis. In physiopathological conditions such as cancer, apoptotic processes become deregulated, leading to apoptosis-resistant phenotypes. Recently, perturbations of cellular calcium homeostasis have been described in apoptosis-resistant cell phenotypes. Thereby, new molecular actors have been identified, offering more accurate research possibilities in the field of apoptosis resistance and providing the bases for more rational approaches to cancer treatments. In this review, we focus on the calcium-transporting protein-dependent pathways involved in apoptosis, which are deregulated by cancer. We present the calcium-transporting proteins involved in the deregulation of apoptosis, and those chemotherapies that target actors in calcium-induced apoptosis.