Nonsteroidal anti-inflammatory drugs are a class of analgesics that includes traditional nonselective and selective cyclooxygenase-2 inhibitors that block the biosynthesis of prostaglandins and thromboxane. Indomethacin is a nonsteroidal anti-inflammatory drug with potent antipyretic, analgesic, and anti-inflammatory activity that has been effectively used in the management of mild-to-moderate pain since the mid-1960s. It is commonly prescribed for the relief of acute gouty arthritis pain, but has demonstrated efficacy in the treatment of various other painful conditions. Numerous comparative studies have affirmed the clinical utility of indomethacin relative to other widely used analgesics. This review provides an historic overview of indomethacin and its efficacy compared with other commonly used analgesics, and discusses new indomethacin drug products.