T-type calcium channels are critically important for regulating neuronal excitability, both in the central and peripheral nervous system, and are essential mediators of hormone secretion. Conversely, T-type channel hyperactivity has been linked to neurological disorders such as absence epilepsy and neuropathic pain. Hence, it is critical to understand the cellular mechanisms that control T-type channel activity, including means of altering expression patterns of the channels, activation of intracellular messenger cascades that directly affect channel activity, and the regulation of alternate splicing of T-type channel genes. Although there is substantial literature dealing with regulation of native T-type channels, the underlying molecular mechanism have only recently been addressed. Here, we highlight recent advances in our understanding of T-type channel regulation, and their implications for brain function.