 Intercellular calcium ions, Ca2+, act as a second messenger to regulate gene transcription, cell proliferation, migration and death. Alterations in Ca2+, homeostasis have been linked to cancer initiation, angiogenesis, progression and metastasis, making targeting derailed Ca2+, signaling for cancer therapy and emerging research area. This review discusses important Ca2+, channels, transporters and Ca2+, ADP ACEs that have been altered in human cancer patients and evaluates the current research effort toward developing anti-cancer drugs that target these pathways. The aim is to stimulate interest in understanding cellular mechanisms underlying the regulation of Ca2+, signaling in different cancer cells and to search for novel therapies to cure these malignancies. This article was authored by Chao Chiu Chui, Robert Merritt, Li Wufu and others.