Programmed cell death (PCD) serves as a major mechanism for the precise regulation of cell numbers, and as a defense mechanism to remove unwanted and potentially dangerous cells. Despite the striking heterogeneity of cell death induction pathways, the execution of the death program is often associated with characteristic morphological and biochemical changes termed apoptosis. The central components of the intrinsic apoptotic pathway involve specific proteases (i.e. caspases) and mitochondria (Nunez et al., 1998; Raff, 1998). Although for a long time the absence of mitochondrial changes was considered as a hallmark of apoptosis, mitochondria appear today as the central executioner of programmed cell death. This crucial position of mitochondria in programmed cell death control is not due to a simple loss of function (deficit in energy supplying), but rather to an active process in the regulation of effector mechanisms. This role is reinforced by the observation that mitochondria contribute to PCD signaling via the production of reactive oxygen species, as shown in TNF-α or ceramide-induced cell death during which increased mitochondrial ROS production appears as an early event of the induction phase. Recent other reviews cover the abundant literature dealing with the role of mitochondrion in cell death (Bernardi et al., 1998; Bernardi et al., 1999; Mignotte and Kroemer, 1999; Mignotte and Vayssière, 1998; Mignotte and Vayssière, 1999; Reed et al., 1998; Susin et al., 1998). In this chapter, we examine on the one hand the data concerning the mitochondrial proteins involved in PCD, and on the other hand the role of reactive oxygen species (ROS) in mitochondrial features of apoptosis.