Nonsteroidal anti-inflammatory drugs (NSAIDs) are the first choice in the treatment of rheumatic disorders and other degenerative inflammatory diseases. There are numerous types of these drugs, and one of them, indomethacin, is highlighted in this paper. With its analgetic, antipyretic and anti-inflammatory properties, it is one of the most powerful drugs used in various clinical trials and therapies related to the mechanism of blocking prostaglandin synthesis, thus reducing and eliminating many inflammatory conditions of patients. To ensure the efficacy and safety of this drug in pharmaceutical and clinical use, particular product quality control is required. Such control is performed with routine pharmaceutical analysis using various chemical methods by which indomethacin is identified as a separate active ingredient in a multicomponent system of a complete pharmaceutical form. In addition, the determination of indomethacin is important in clinical practice, where its concentration is determined in different biological samples, ensuring better monitoring of a particular therapy. The most commonly used methods for the determination of indomethacin are: potentiometry, voltammetry, high performance liquid chromatography (HPLC), gas chromatography (GC), UV spectroscopy, colorimetry, fluorimetry, chemiluminescence and immunochemical methods (ELISA and radioimmunoassay). Each of these methods must provide precise validation parameters. For indomethacin determination, two methods are usually combined, this way more precise results and safer application in practice are achieved.