A gradual diminution in the physiologic reserve or functional capacity over time is the characteristic hallmark of aging, and this has a direct impact on the choice of cancer therapy and its toxicity profile in elderly patients with cancer. With the expected rapid rise of the older population as a subgroup, oncologists will increasingly treat elderly patients. Provision of competent care to this increasing pool of older patients with cancer necessitates that oncology professionals become familiar with age-associated changes in organ physiology and their impact on cancer treatment and toxicity. In this comprehensive review, we have listed changes in cardiovascular, gastrointestinal, pulmonary, and renal physiology with aging. Also enumerated is the impact of these changes on cancer therapy and toxicity in each organ system-based section. Cardiovascular changes primarily lead to reduction of the cardiac functional reserve, with a consequent increase in the risk of congestive heart failure. Changes in gastrointestinal physiology lead to increased mucosal damage. A reduction in pulmonary reserve has implications for postradiation complications, and a decline in renal function leads to an increased potential for nephrotoxicity. These changes impair the ability of older patients with cancer to tolerate cancer therapy and increase their risk of toxicities. This may lead to an overall decline in functional status, resulting frailty, poor quality of life, and ultimately poor outcomes. Becoming familiar with age-related physiologic changes is the first step for oncologists seeking to better tailor their treatments. This, combined with adoption of some of the clinical interventions suggested in this review, can help better manage the geriatric oncology patient. Further research is necessary for the development of more specific evidence-based recommendations.