The ability of malignant cells to metastasize from a primary tumor and from secondary lesions is the most life-threatening aspect of cancer. Reported factors enabling this metastatic cascade to occur include reduced levels or an absence of cell-adhesion molecules, proteolytic enzymes, and angiogenic factors. The metastatic cell must also escape immune destruction. Defects in lymphocytes from renal-cell carcinoma patients with abnormalities in their proliferation, receptor structure, and signal transduction are present. The pathologic stage has been the most consistent single prognostic factor to influence survival. Other factors include the performance status, age, and histology grade and may include serum interleukin 6 (IL-6) levels and ploidy. Current and future therapeutic approaches that interfere with this metastatic cascade include applications of cytokines, antiadhesion-molecule strategies, and antisense nucleotides. An improvement in our understanding of the biology of metastases is essential before a significant increase in the cure rate can be realized.