Evidence from recent publications indicates that repeated exercise may enhance the quality of life of cancer patients. The lack of reported negative effects and the consistency of the observed benefits lead one to conclude that physical exercise may provide a low-risk therapy that can improve patients’ capacity to perform activities of daily living and improve their quality of life. Repeated physical activity may attenuate the adverse effects of cancer therapy, prevent or reverse cachexia, and reduce risk for a second cancer through suppression of inflammatory responses or enhancement of insulin sensitivity, rates of protein synthesis, and antioxidant and phase II enzyme activities. These results most likely come about through the ability of physical exercise to attenuate a chronic inflammatory signaling process and to transiently activate the mitogen-activated protein kinase, cJun NH2-terminal kinase, c-Jun NH2-terminal kinase-mitogen-activated protein kinase, and nuclear factor-κB pathways and through its ability to enhance insulin sensitivity. Expanded molecular-based research into these areas may provide new insights into the biological mechanisms associated with cancer rehabilitation and endogenous risk.