Ibuprofen was the first non-aspirin non-steroidal antiinflammatory drug (NSAID) to be approved for over-the-counter (OTC) use and is widely considered to be the best tolerated drug of its class. Low-dose, OTC ibuprofen has been used for pain relief for over 30 years without any obvious major health issues. However, there is no clear differentiation between the OTC and prescription doses of ibuprofen, and their respective effects. Adverse reactions to ibuprofen appear to be dose and duration dependent, and this may be the reason for the observed tolerability of the drug at OTC doses. OTC ibuprofen is at least as effective as aspirin and more effective than paracetamol. The tolerability concerns associated with higher dose NSAIDs currently do not apply to low-dose, short-term use of ibuprofen for common pain. Ibuprofen is associated with the least risk of GI complications compared with other NSAIDs and is considered relatively benign in overdose. This review will aim to distinguish the safety of OTC or non-prescription use of ibuprofen from its prescription use.