Mitochondrial Ca(2+) homeostasis is today at the center of wide interest in the scientific community because of its role both in the modulation of numerous physiological responses and because of its involvement in cell death. In this review, we briefly summarize a few basic features of mitochondrial Ca(2+) handling in vitro and within living cells, and its involvement in the modulation of Ca(2+)-dependent signaling. We then discuss the role of mitochondrial Ca(2+) in the control of apoptotic death, focusing in particular on the effects of pro- and anti-apoptotic proteins of the Bcl-2 family. Finally, the potential involvement of Ca(2+) and mitochondria in the development of two diseases, Ullrich muscular dystrophy and familial Alzheimer's disease, is briefly discussed.