Non-steroidal anti-inflammatory drugs (NSAIDs) are reversible inhibitors of cyclo-oxygenase (COX), mainly used for the symptomatic relief of pain, whether traumatic, infectious, episodic or rheumatologic. Use for the long-term relief of inflammation is waning with the emergence of specific biotherapies. Their effects are related to potency, dosage, and pharmacokinetic or galenic considerations. Adverse reactions are mostly related to COX inhibition, and to the relative COX1 and COX2 inhibition. Over the years have resulted in the withdrawal of some NSAIDs. The most common adverse reactions are: gastrointestinal (COX1) which have declined over time with the emergence of more COX1 sparing drugs and gastroprotection; renal, with an impact on renal function and sodium extraction that is associated with hypertension, heart failure exacerbation, and stress-related renal failure; allergic skin reactions; increased transaminases and acute liver injury which may be idiosyncratic or immunoallergic; increased risk of acute coronary syndromes, initially associated with high-dose long-term use of COX2 specific inhibitors in controlled clinical trials, though more recently there have been indications from poorly controlled observational studies that they could occur with most NSAIDs. Event rates in patients with no overt coronary heart disease are vanishingly low, and the real magnitude of the issue in the treatment of common pain is still unknown. Considering their purely symptomatic effects, they should be used at the lowest possible dose for the shortest possible time, based on the symptomatic relief of pain or fever.