Emerging therapies for the treatment of cancer rely on detailed knowledge of cell growth mechanisms. It is hoped that mechanism-based inhibitors will prove more effective and exhibit fewer side effects than current treatments. Among the first, non-cytotoxic anticancer agents to enter clinical trials are the farnesyl protein transferase inhibitors, which prevent attachment of the farnesyl isoprenoid side chain to Ras. This post-translational modification is essential for the function of Ras, a protein exhibiting unregulated activity in nearly one-third of human cancers. Here structural studies of farnesyl protein transferase and strategies for discovery of its inhibitors are reviewed.