Pharmacotherapy in the elderly is very complex owing to age-related physiologic changes, the presence of multiple comorbidities, the use of multiple medications, the involvement of multiple prescribers and pharmacies, and an increased prevalence of cognitive deficits. The treatment of cancer and the management of symptoms related to therapy-induced toxicity significantly add to this complexity, with an increased risk of drug interactions, using potentially inappropriate medications (PIMs), and adverse drug reactions. There are several ways to evaluate inappropriate prescribing, with various levels of support for their use. We review the most widely used. Older adults are more susceptible than younger ones to chemotherapy toxicity, and may require dose modifications. Before starting therapy, the goals of care should be clearly defined and the general state of the patient should be assessed using some form of geriatric evaluation. Changes in the pharmacokinetics of the drugs related to aging and the possibility of end-organ dysfunction must be taken into consideration, particularly the age-related decline of glomerular filtration rate that is not always reflected by an increase in serum creatinine. The treatment plan for the older adult needs to be carefully defined in order to prevent adverse events, and allow the patient to benefit from treatment without a major impact on quality of life.