In both humans and animals, an insult to the brain can lead, after a variable latent period, to the appearance of spontaneous epileptic seizures that persist for life. The underlying processes, collectively referred to as epileptogenesis, include multiple structural and functional neuronal alterations. We have identified the T-type Ca²⁺channel Ca_v3.2 as a central player in epileptogenesis. We show that a transient and selective upregulation of Ca_v3.2 subunits on the mRNA and protein levels after status epilepticus causes an increase in cellular T-type Ca²⁺currents and a transitional increase in intrinsic burst firing. These functional changes are absent in mice lacking Ca_v3.2 subunits. Intriguingly, the development of neuropathological hallmarks of chronic epilepsy, such as subfield-specific neuron loss in the hippocampal formation and mossy fiber sprouting, was virtually completely absent in Ca_v3.2^−/−mice. In addition, the appearance of spontaneous seizures was dramatically reduced in these mice. Together, these data establish transcriptional induction of Ca_v3.2 as a critical step in epileptogenesis and neuronal vulnerability.