Seemingly harmless prescriptions, often written in primary care, can lead to life-threatening clinical situations if potential drug interactions are overlooked. This presentation highlights clinically important drug interactions that may occur with medications commonly prescribed in primary care.Three representative cases scenarios were constructed. The cases were developed based on standard pharmacology textbooks (see “References”). The approval of an Ethics Committee was not required. References: Brunton, L. L., Hilal-Dandan, R., & Knollmann, B. C. (Eds.). (2017). Goodman & Gilman’s the pharmacological basis of therapeutics (13th ed.). McGraw-Hill Education. Katzung, B. G., Trevor, A. J., & Kruidering-Hall, M. (2017). Basic and clinical pharmacology (14th ed.). McGraw-Hill Education.It highlights foreseeable but often overlooked risks.Case 1: A patient who is prescribed clarithromycin. If the patient is concomitantly using a statin, myopathy and even rhabdomyolysis may develop. Macrolides reduce hepatic metabolism of statins, thereby increasing their adverse effects which may lead to myopathy. Case 2: A patient who is prescribed omeprazole. If the patient is using clopidogrel, an increased risk of thrombosis may occur. Omeprazole inhibits hepatic activation of clopidogrel, increasing the risk of thrombotic events. Case 3: A patient who is prescribed acetaminophen. If there is a history of chronic alcohol use, acute liver injury may develop. Chronic alcohol use increases the formation of toxic metabolites of acetaminophen.The presented cases demonstrate that some risks can be anticipated through brief and focused history taking.Prescriptions that appear simple in primary care may lead to serious outcomes if the patient’s ongoing treatments and clinical history are not adequately assessed. A basic awareness of drug interactions combined with targeted history taking is an effective and low-cost strategy for preventing avoidable adverse effects.