The past decade has seen an intense focus on mechanisms of apoptosis. Many important observations on the various signaling pathways mediating apoptotic cell death have been made and our understanding of the importance of apoptosis in both normal growth and development and pathophysiology has greatly increased. In addition, mechanisms of metal-induced toxicity continue to be of interest given the ubiquitous nature of these contaminants. The purpose of this review is to summarize our current understanding of the apoptotic pathways that are initiated by metals, mainly established (arsenic, cadmium, chromium, nickel, beryllium) and possible (lead, antimony, cobalt) human carcinogens. Increased understanding of metal-induced apoptosis is critical to illuminate mechanisms of metal-induced carcinogenesis, as well as the potential of metal species (arsenic) as chemotherapeutic agents.