This review summarizes recent advances in our understanding of neuronal T-type calcium channel regulation as well as their physiological and pathophysiological roles. Through their ability to conduct calcium across the cellular membrane at potentials close to the resting potential, T-type calcium channels are critically important for regulating neuronal excitability, both in the central and peripheral nervous system. T-type channels are also linked to an increasing number of neurological disorders such as the absence epilepsy and neuropathic pain. Although there is substantial literature dealing with regulation of native T-type channels, the underlying molecular mechanism has only recently been addressed. It is, therefore, critical to understand the cellular mechanisms that control T-type channel activity and expression, because this could provide important insight into designing novel therapeutic strategies targeting these channels.