Few genetic markers are used routinely to predict clinical effectiveness and toxic effects despite the fact that physicians and their patients are consistently confronted with this balance. Because one of the goals of pharmacogenomics is to identify individuals and target populations that might have adverse outcomes, pharmaceutical companies have been reluctant to use a strategy that might identify patients who are not eligible for a particular treatment. This view is changing because drug-discovery programmes and treatments that target specific pathways, are showing improvements in surrogate and survival endpoints. HIV and cancer are now regarded as chronic diseases, which commonly need life-long systemic treatment from the time of diagnosis. HIV and cancer medicine have used pharmacogenomics to some extent in clinical care. Common and classic features of pharmacogenomics that are related to both antiretroviral treatment and to cytotoxic treatment are discussed in this review, providing a framework for individual treatment of these diseases.