Clinical pharmacogenetics, the use of genetic data to guide drug therapy decisions, is beginning to be used for medications commonly prescribed by family physicians. However, clinicians are largely unfamiliar with principles supporting clinical use of this type of data. For example, genetic variability in the cytochrome P450 2D6 drug metabolizing enzyme can alter the clinical effects of some opioid analgesics (e.g., codeine, tramadol), whereas variability in the CYP2C19 enzyme affects the antiplatelet agent clopidogrel. If testing is performed, patients who are ultrarapid or poor metabolizers of CYP2D6 should avoid codeine use (and possibly tramadol, hydrocodone, and oxycodone) because of the potential for increased toxicity or lack of effectiveness. Patients undergoing percutaneous coronary intervention for acute coronary syndromes who are known to be poor metabolizers of CYP2C19 should consider alternate antiplatelet therapy (e.g., ticagrelor, prasugrel). Some guidelines are available that address appropriate drug therapy changes, and others are in development. Additionally, a number of clinical resources are emerging to support family physicians in the use of pharmacogenetics. When used appropriately, pharmacogenetic testing can be a practical tool to optimize drug therapy and avoid medication adverse effects.