This review deals with anticancer drugs with activity against signaling targets that have been studied in cancer patients. The major categories of drugs studied so far are modulators of the activity of protein kinase C, inhibitors of protein kinase A, protein tyrosine kinase, and receptor-operated Ca2+ channels. Drugs that may modulate ras function have also been studied. None of the agents have yet received extensive clinical trials. Toxicities and anecdotal cases of antitumor activity have been reported. There are a number of other anticancer drugs with activity against signaling targets awaiting clinical trial.