BCL-2 family members are pivotal regulators of the apoptotic process. Mitochondria seem to be a major site-of-action for these proteins. Several prominent alterations occur to mitochondria during apoptosis that include the release of intermembrane space molecules, changes in the membrane potential, ionic changes, and more. All these changes seem to be part of the mitochondrial apoptotic process. The BCL-2 family members are believed to be the major regulators of this program; however, their exact mechanism of action still remains a mystery. In addition, the exact contribution of mitochondria to the apoptotic process is still unclear. This review summarizes and examines the current knowledge regarding these two issues.