Renal cell carcinoma remains a challenge to clinical medicine, with curative therapy experienced by a minority of patients. Mounting evidence suggests that the biological response modifiers, which consistently produce durable responses in some patients, may not need to be given in the high doses that have been associated with considerable, even fatal, toxicity; low-dose regimens in combination with conventional chemotherapeutic agents are yielding comparable, and possibly superior, results. Molecular biologic techniques have now advanced to the point where better classification schemes and prognostic variables are being elucidated, which may allow better optimization of specific treatment programs by allowing better patient discrimination. Further, with a better understanding of the molecular mechanisms of renal carcinogenesis, new agents and approaches to the problem of advanced renal cell carcinoma can be developed.