Prostate cancer (PCa) is the most diagnosed cancer among men. Discovering novel prognostic biomarkers and potential therapeutic targets are critical. Calcium signaling has been implicated in PCa progression and development of treatment resistance. Altered modification of Ca2+ flows leads to serious pathophysiological processes, such as malignant transformation, tumor proliferation, epithelial to mesenchymal transition, evasion of apoptosis, and treatment resistance. Calcium channels control and contribute to these processes. PCa has shown defective Ca2+ channels, which subsequently promotes tumor metastasis and growth. Store-operated Ca2+ entry channels such as Orai and STIM channels and transient receptor potential channels play a significant role in PCa pathogenesis. Pharmacological modulation of these calcium channels or pumps has been suggested as a practical approach. In this review, we discuss the role of calcium channels in PCa development and progression, and we identify current novel discoveries of drugs that target specific calcium channels for the treatment of PCa.Copyright © 2023. Published by Elsevier B.V.