Voltage-gated T-type Ca ²⁺ channels (T-channels) are normally expressed during embryonic development in ventricular myocytes but are undetectable in adult ventricular myocytes. Interestingly, T-channels are reexpressed in hypertrophied or failing hearts. It is unclear whether T-channels play a role in the pathogenesis of cardiomyopathy and what the mechanism might be. Here we show that the α _1H voltage-gated T-type Ca ²⁺ channel (Ca _v 3.2) is involved in the pathogenesis of cardiac hypertrophy via the activation of calcineurin/nuclear factor of activated T cells (NFAT) pathway. Specifically, pressure overload–induced hypertrophy was severely suppressed in mice deficient for Ca _v 3.2 (Ca _v 3.2 ^−/− ) but not in mice deficient for Ca _v 3.1 (Ca _v 3.1 ^−/− ). Angiotensin II–induced cardiac hypertrophy was also suppressed in Ca _v 3.2 ^−/− mice. Consistent with these findings, cultured neonatal myocytes isolated from Ca _v 3.2 ^−/− mice fail to respond hypertrophic stimulation by treatment with angiotensin II. Together, these results demonstrate the importance of Ca _v 3.2 in the development of cardiac hypertrophy both in vitro and in vivo. To test whether Ca _v 3.2 mediates the hypertrophic response through the calcineurin/NFAT pathway, we generated Ca _v 3.2 ^−/− , NFAT-luciferase reporter mice and showed that NFAT-luciferase reporter activity failed to increase after pressure overload in the Ca _v 3.2 ^−/− /NFAT-Luc mice. Our results provide strong genetic evidence that Ca _v 3.2 indeed plays a pivotal role in the induction of calcineurin/NFAT hypertrophic signaling and is crucial for the activation of pathological cardiac hypertrophy.