The B-RAF kinase is a downstream effector of the RAS family of proto-oncogenes and is constitutively activated in the majority of human melanomas. The common oncogenic B-RAF(V600E) mutant cooperates with additional genetic lesions to transform immortal murine and human cells. In primary cells, however, B-RAF(V600E) triggers a rapid cell cycle arrest that is phenotypically indistinguishable from cellular senescence. Here we describe the analyses of B-RAF-induced senescence in primary human melanocytes using recombinant lentiviruses.