Twenty-five years ago treatment for metastatic renal cancer was generally ineffective. Over the intervening period, cytokines such as interferon-alpha and interleukin-2 gained prominence in the treatment of metastatic renal cancer. These agents produced clinical responses in a minority of patients with metastatic renal cancer, albeit with substantial toxicity. Over the last 3 years, there has been a substantial increase in our understanding of kidney cancer at the molecular level. This has led to major breakthroughs in the management of this once untreatable disease. Substantial gains in progression free and overall survival have occurred as a consequence. This issue of The Cancer Journal has been devoted to reviewing clinical progress in the treatment of metastatic renal cancer, with an eye toward current needs and the likely future directions of the field.