The role of protein tyrosine kinases (PTKs) in the survival of cancer cells and their potential use in anticancer therapy has led to their selection as anticancer drug targets. Tyrosine kinases which are being studied for this purpose include epidermal growth factor receptor (EGFR) (1–6), Janus kinases (JAKs) (7–13), Bruton’s tyrosine kinase (BTK) (14–16), platelet-derived growth factor (PDGF) (17), protein kinase C (PKC) (18–24), Lck (25, 26), Trk (27–30), and others. The strategies used to attenuate or disable kinases implicated in cancer include the use of antibodies, immunoconjugates, ligand-binding cytotoxic agents, and small-molecule inhibitors. Each of these strategies has shown some promise for the treatment of cancer. Herceptin (31–35), for example, is an immunotherapeutic agent that binds to the extracellular domain of HER2 (also referred to as ErbB-2, a tyrosine kinase belonging to the same family as EGFR) at nanomolar levels. EGF-genistein (EGF-gen) is an EGFR-binding cytotoxic agent that also shows potency in the nanomolar range (2, 36) and will be discussed in this chapter. The search for new small molecules that inhibit kinases has involved traditional approaches, including the testing of natural products, random screening of chemical libraries, the use of classical structure-activity relationship studies, and the incorporation of structure-based drug design approaches and combinatorial chemistry techniques. As a result, several promising small-molecule inhibitors have also been identified in recent years that may prove useful as potent new anticancer drugs.