Plants have traditionally represented a main source for the discovery of many biologically active substances with therapeutic values. Sulfur-containing compounds exhibit pleiotropic biological effects supporting their potential use in multitargeted cancer prevention and treatment. As potential anti-cancer agents, they have been shown to inhibit or retard the growth of various cancer cells in culture and implanted tumors in vivo. The compounds significantly inhibit experimental tumorigenesis in a wide range of animal models. A critical and well-elucidated cellular mechanism involved in the anticancer activities of sulfur-containing compounds is the induction of apoptosis through the fine-tuning of orchestrated intracellular signal transduction. This review summarizes the established proapoptotic activities of sulfur-containing compounds in malignant and nonmalignant cells with a special focus on their molecular mechanisms. The potential toxicological implications of proapoptotic effects on normal cells will also be discussed.