Arsenic, a known carcinogen, may be useful in cancer treatment. Arsenic may be effective in counteracting drug resistance because it appears to induce apoptosis in tumor cells independently of p53 activation, thereby allowing it to be directed against p53-defective cancers. The role of MAP kinases in arsenic-induced apoptosis in tumor cells is important and may be influenced by reactive oxygen species or glutathione. This review focuses on recent findings from this and other laboratories regarding the mechanism(s) of arsenic-induced apoptosis in tumor cells and considers their relevance in the clinical treatment of therapy-resistant cancers. Copyright 2000 Harcourt Publishers Ltd.