This review explores the effectiveness and safety of cancer chemotherapy in older individuals and outlines potential guidelines for the management of these patients. Cancer chemotherapy appears less effective in three neoplasms of older individuals: acute myelogenous leukemia, large cell lymphoma, and coelomic carcinoma of the ovary. In the case of acute myelogenous leukemia, a higher prevalence of MDR-1 expression and involvement of the pluripotent hematopoietic stem cells in the neoplastic process contribute to chemotherapy resistance. Chemotherapy-related myelodepression, cardiotoxicity, and peripheral and central neurotoxicity are more common and more severe in older individuals. This toxicity results from the increased vulnerability of target organs and delayed excretion of renally excretable agents. The complications of chemotherapy may be ameliorated by modifying the doses of drugs according to the patient's creatinine clearance, by using antidotes to drug toxicity, and by the early diagnosis and timely management of therapeutic complications. A comprehensive assessment of the older person with cancer allows clinicians to predict the benefits and risks of cancer chemotherapy in individual circumstances.