Cancer is one of the major causes of morbidity and mortality in the world. Carcinogenesis is a multistep process induced by genetic and epigenetic changes that disrupt pathways controlling cell proliferation, apoptosis, differentiation, and senescence. In this context, many bioactive dietary compounds from vegetables and fruits have been demonstrated to be effective in cancer prevention and intervention. Over the years, sulforaphane (SFN), found in cruciferous vegetables, has been shown to have chemopreventive activity in vitro and in vivo. SFN protects cells from environmental carcinogens and also induces growth arrest and/or apoptosis in various cancer cells. In this review, we will discuss several potential mechanisms of the chemopreventive activity of SFN, including regulation of Phase I and Phase II drug-metabolizing enzymes, cell cycle arrest, and induction of apoptosis, especially via regulation of signaling pathways such as Nrf2-Keap1 and NF-κB. Recent studies suggest that SFN can also affect the epigenetic control of key genes and greatly influence the initiation and progression of cancer. This research may provide a basis for the clinical use of SFN for cancer chemoprevention and enable us to design preventive strategies for cancer management, reduce cancer development and recurrence, and thus improve patient survival.