A range of compounds in or derived from the diet modulates apoptosis in cell cultures in vitro. These observations have important implications concerning the mechanisms whereby dietary components affect health. Proapoptotic compounds could protect against cancer by enhancing elimination of initiated, precancerous cells, and antiapoptotic compounds could promote tumor formation by inhibiting apoptosis in genetically damaged cells. Proapoptotic compounds could also contribute to age-related degenerative diseases by activating cell death in postmitotic cells or shifting the normal balance of mitosis and apoptosis in tissues with regenerative capacity. Many age-related diseases, for example macular degeneration and Parkinson's disease, appear to have oxidative stress as an underlying component that interacts with genetic, dietary, and environmental factors to determine relative risk in an individual. Oxidative stress activates apoptosis, and antioxidants protect against apoptosis in vitro; thus, a central role of dietary antioxidants may be to protect against apoptosis. However, little in vivo data are available to directly link diet with altered apoptosis as an underlying determinant of disease. Moreover, the possible antagonistic effects of different dietary components and the uncertainty about whether proapoptotic compounds that may protect against cancer could contribute to degenerative diseases and vice versa indicate that there is a great need for better in vivo assessment of apoptosis and that caution should be exercised when extrapolating in vitro data on apoptosis to in vivo dietary recommendations.