In addition to well-known cytotoxic agents in the treatment of cancer, promising novel cytotoxic and biologic agents are being investigated. The combination of classical cytotoxic drugs or radiotherapy, along with these new molecules specifically targeted at numerous points in intracellular signalling, cell cycle control, and the cancer cell environment, represents our best hope for improved outcome in systemic cancer therapy. This report summarizes the phase I clinical studies with these novel anticancer agents, performed and supervised the last ten years by the author at the chemotherapy unit of the Jules Bordet Institute.