The last thirty years have witnessed major improvements in the survival of pediatric cancer patients. This has been due to improvements in the various modalities of cancer therapy as well as improvements in supportive care. Historically, cancer treatments have been developed in an empiric fashion and amplified to the limits of tolerance. As more is learned about the biology of oncogenesis, we hope it will become possible to design therapies to deal with the unique mechanisms involved in the development of specific types of cancer. These rational approaches to cancer therapy should improve efficacy and diminish the risks of toxicity. The era of "designer drugs" is just beginning with the introduction of therapeutic monoclonal antibodies against tumor antigens, and new small molecules that target specific tumors, such as retinoids and imatinib mesylate. This presentation will review these advances and provide a perspective on potential future directions in this field.