Epidemiological and dietary studies have revealed an association between high intake of cruciferous vegetables and decreased cancer risk cancer. Sulforaphane, a phytochemical constituent of cruciferous vegetables, has received much attention as a potential cancer chemopreventive compound. Recent advances in the cellular and molecular biology of cancer have shed light on components of intracellular signaling cascades that can be molecular targets of chemoprevention by various anti-cancer agents. Metallothionein (MT), a primary antioxidant enzyme involved in the metabolism and detoxification of heavy metal, has been recognized as a molecular target for chemoprevention by natural anti-cancer agents, but the cellular signaling mechanisms that associate MT gene regulation are not yet clearly understood. Recent studies suggest that Nrf2-mediated signaling, which controls the expression of many of genes responsible for carcinogen detoxification and protection against oxidative stress, is regulated by sulforaphane. This contribution focuses on Nrf2-mediated signaling pathways, particularly in relation to MT gene induction and the apoptosis-inducing effects of sulforaphane.