Inactivation of the INK4a/ARF (or CDKN2a) locus is a common and critical genetic event in the development of human and mouse melanoma. This locus engages the Rb and p53 tumor suppressor pathways through its capacity to encode two distinct gene products, p16(INK4a) and p14(ARF). This review highlights the body of evidence supporting a role for both p16(INK4a) and p14(ARF) in the suppression of melanoma, and speculates as to why this locus is preferentially targeted in this tumor type. In addition, the potential importance of these two pathways in mediating UV-induced melanoma genesis will be addressed via genetic and molecular evidence in the mouse.