This paper provides a rational molecular basis for studies intended to clanfy the interactions between cancer chemopreventive agents and apoptosis, one of the natural forms of cell death that overlaps molecular mechanisms with other forms such as programmed cell death and specialized forms of physiological cell death. Molecular details of the process show the existence of distinct molecular pathways leading to the activation of critical effector elements (apoptosis gene products) functioning under the control of a network of negative regulatory elements. Dysregulation of either apoptosis or anti-apoptosis genes has a significant role in multistage carcinogenesis. Inhibition of apoptosis is one of the underlying mechanisms of the action of tumor promoters. The network of apoptosis and antiapoptosis gene products provides multiple targets for compounds with cancer chemopreventive potential. Many data in the literature show initiating, potentiating or inhibitory effects of such compounds on apoptosis. However, the molecular mechanism of these effects is largely unknown. We initiated a series of studies using mouse thymocytes which undergo apoptosis through distinct molecular mechanisms after T-cell receptor activation (TCR pathway), following the addition of glucocorticoids (DEX pathway) or DNA damaging agents (p53 pathway). All trans-and 9-cis-retinoic acid induced apoptosis, elicited through the DEX pathway, inhibited the TCR pathway, and did not affect p53-initiated apoptosis. N-acetylcysteine can inhibit all forms. Sodium salicylate enhanced spontaneous cell death, decreased p53-dependent apoptosis, and did not affect the DEX and TCR pathways. These preliminary results, which show differential effects of the studied compounds on distinct molecular pathways of apoptosis, warrant further investigations in the effort to utilize the molecular elements of apoptosis in proper cancer chemoprevention, and find biochemical targets for apoptosis-related surrogate endpoint biomarker assays of chemoprevention.