Topical nonsteroidal anti-inflammatory drugs (NSAIDs) have an emerging role in the treatment of certain types of acute pain. In addition to their convenience, efficacy, and safety, they are an attractive option, particularly when considering current concerns about the safety of traditional NSAIDs and cyclooxygenase-2 (COX-2) inhibitors (coxibs). Topical analgesics act largely within the peripheral nervous system. Studies have demonstrated that topical NSAIDs penetrate the skin and distribute to the target tissues underlying the application site. Because the pharmacologically effective dose is delivered at the site of pain, there is minimal systemic absorption and risk of related adverse events. Topical NSAIDs have been used for many years in Europe, with extensive post-marketing data available for some of the agents. Three topical NSAID formulations have recently been approved for use in the United States: the diclofenac epolamine topical patch 1.3% (DETP), diclofenac sodium 1% gel, and diclofenac sodium topical solution 1.5%. Topical NSAIDs provide a therapeutic option for treatment of acute, localized, soft tissue injuries or painful conditions in areas of the body that can be readily treated using the topical route of administration. This article reviews available data on the use of topical NSAID therapy.