Prenylation of proteins with polyisoprenoids is a functionally important post-translational modification that plays a major role in cell proliferation of both normal and cancerous cells. Earlier studies showed prenylation on certain fungal mating factor peptides, and the study of compactin's effects led to the discovery of mammalian protein prenylation, with lamin B being the first identified mammalian protein undergoing prenylation. Examination of peptide sequences of lamin B (CAIM) and yeast a-factor (CVIA) revealed a CAAX motif (C for cysteine, A for any aliphatic amino acid, X variable) at the carboxy terminus, which is critical for isoprenoid addition. A series of proteins including the Ras family (e.g., Ras, Rho, Rab) undergo prenylation. The discovery that Ras proteins require farnesyl modification for oncogenic transformation has driven intense research on post-translational prenylation in proliferative diseases. This Perspective discusses the Ras protein family, particularly Ras farnesyltransferase, and notes that inhibitors of Ras processing have emerged as a novel class of pharmaceutical agents with therapeutic utility in a range of abnormal proliferative diseases.