Pain is one of the most common clinical symptoms and represents a significant reason for patients to seek medical assistance. Effective pain management requires an individualized approach based on the underlying cause, intensity, duration, and clinical characteristics of the pain syndrome. Non-steroidal anti-inflammatory drugs (NSAIDs) occupy an important position in modern pharmacotherapy because of their analgesic, anti-inflammatory, and antipyretic properties. These medicines are widely used in the management of musculoskeletal pain, inflammatory diseases, postoperative pain, headache, dental pain, dysmenorrhea, and various acute and chronic pain syndromes. However, their therapeutic benefits must be balanced against potential gastrointestinal, renal, cardiovascular, hepatic, and allergic adverse effects. The purpose of this article is to analyze the pharmacological role of NSAIDs in pain management, describe their principal mechanisms of action, clinical applications, advantages and limitations, and discuss approaches aimed at improving the safety and rationality of NSAID therapy. Particular attention is given to individual patient characteristics, risk assessment, appropriate drug selection, dosage, duration of treatment, and prevention of adverse reactions. Rational NSAID use should be considered an integral component of evidence-based pharmacotherapy and should be accompanied by continuous evaluation of treatment effectiveness and safety.