The role of nonsteroidal antiinflammatory drugs (NSAID) in pain and inflammation has been evaluated in many forms over the last decade. Emerging evidence shows that this class of medications has different effects depending on injury type: bone, ligament, tendon, and muscle. There are no clear guidelines about specific NSAID choice, duration of use, or route of administration. Benefit of therapy must be weighed against the side effects of NSAID, specifically with respect to the gastrointestinal and renal systems. It is clear that the side effect profile changes within the subclasses of NSAID, nonspecific cyclo-oxygenase-1 and 2 (COX-1 and COX-2) inhibitors, and more selective COX-2 inhibitors. Safe and effective alternatives may include topical NSAID and acetaminophen.