Non-steroidal, anti-inflammatory drugs are the most widely used remedies worldwide. Drug interactions are frequent, life threatening ones are rare: Bleeds on the basis of inhibition of platelet aggregation and loss of organ protection (GI-tract), thrombotic events due to loss of vasoprotection and increased propensity for blood coagulation (stroke), acute kidney failure on the basis of loss of kidney protection by prostaglandins together with stress to the organ and/or drugs interfering with the renal blood flow. Acute liver toxicity is typical for acetaminophen. Whether the risk is increased by other hepatoxic drugs, as diclofenac, is uncertain at present. All risks can be reduced considerably by avoiding problematic drug interactions.