Defective control of apoptosis appears to play a central role in the pathogenesis of human diseases including neoplasic, autoimmune, and neurodegenerative diseases. Conversely, cancer chemotherapy and ionizing radiation can induce cancer cell death by apoptosis, and deregulated apoptosis following cancer chemotherapy could define a new category of drug resistance mechanism. By understanding the role that some major regulators of apoptosis play either at the commitment or execution phases of cell death in a given tissue and pathology, we will be in a better position to design and explore new therapeutic modalities. The Ced-9 - Bcl-like and Ced-3 - Ice-like gene family products are intrinsic proteins regulating the decision of a cell to survive or die and executing part of the cell death process itself, respectively. Among the various Bcl-like proteins, the effects and functions of the Bcl-x and Bax proteins in controlling apoptosis induced by cancer chemotherapy have been studied recently. In human cancer variant cell lines showing differential expression of the Bcl-xL protein, a preventive effect of Bcl-xL on cell death induced by various cytotoxic drugs is observed, with greater effects in cells containing the highest level of Bcl-xL expression. Similarly, overexpression of Bax-alpha in cancer cell lines sensitizes these cells to some cancer chemotherapy compounds. Modulation of apoptosis either negatively by Bcl-xL or positively by Bax-alpha resides downstream of the primary mechanism of action of anticancer drugs, suggesting that they act primarily as intrinsic control points following cytotoxic drug injuries. An emerging family of Ced-3 - Ice like cysteine proteases (caspases) has been also identified and several studies have revealed their importance in executing the process of cell death. More recently, activation of a N-tosyl-L-phenylalanylchloromethyl ketone (TPCK)-sensitive pathway was also suggested to play an important role in apoptosis induction following cancer chemotherapy. Evidence obtained using a combination of assays including cell-free systems and enzyme activity assays now suggests that Bcl-xL and Bax-alpha control points function upstream of TPCK-sensitive protease and caspase activation. Bcl-xL delays and prevents activation of apoptotic protease cascades whereas Bax-alpha shows the opposite effect, accelerating their activation.