Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used for management of inflammation and pain, but they can cause gastrointestinal, cardiovascular, and renal adverse effects. Genetic variations in CYP450 enzymes affect their metabolic activity, thus impacting the hepatic clearance, elimination half-life, and risk of adverse effects of drugs metabolized by that CYP. Celecoxib, ibuprofen, flurbiprofen, meloxicam, and piroxicam are significantly metabolized by CYP2C9. The Clinical Pharmacogenetic Implementation Consortium has published evidence-based recommendations on CYP2C9 polymorphism–based safe usage of NSAIDs. As pharmacogenetics becomes more common, pharmacists will play a critical role in optimizing drug regimens based on pharmacogenetic test results