Low-voltage activated, T-type calcium channels (T-channels) are expressed in many developing tissues and may be important in regulating important cellular phenotype transitions leading to cell proliferation, differentiation, growth and death. The purpose of this review is to relate and delineate the current data on the involvement of T-channels in differentiation and proliferation. Owing to the recent cloning of the CaV3.1, CaV3.2 and CaV3.3 subunits coding for T-channels, classical electrophysiological and pharmacological approaches are now being supported by molecular investigations. As T-channels are expressed in early development as well as re-expressed in several disease-states, our goal is to provide a comprehensive scheme of the current hypothesis connecting the activity of T-channels to cell differentiation and proliferation, as well as the potential physiological and pathophysiological implications.