An overview of the cascade radical annulation approach to the camptothecin family of antitumor drugs is presented. This combinatorial synthetic approach involves two key steps: (1) N-propargylation of a lactone/pyridone D/E ring fragment and (2) cascade radical annulation of an A-ring isonitrile to form rings B and C. The synthesis is probably the most flexible and general route to the camptothecin class of molecules. The parallel synthesis of several libraries of silatecan and homosilatecan libraries is summarized. One of the first-generation silatecans, DB-67, is emerging as a serious candidate for cancer chemotherapy.