Topical nonsteroidal anti-inflammatory drugs are an effective and safe therapeutic option for the treatment of acute and chronic musculoskeletal disorders. Based on evidence from the literature, topical NSAID's have a clearly defined place in the treatment of acute musculoskeletal pain and in the treatment of osteoarthritis of the hands and knees. Due to the rare systemic side effects, they should always be advised as the first therapeutic line for the treatment of musculoskeletal pain in osteoarthritis of the hands and knees of patients ≥75 years of age. It is very important that there are no recommendations for the use of other topical preparations, such as rubefaciens and capsaicin for the treatment of painful musculoskeletal conditions. Clinical assessment of the patient, the condition of medical issue and the choice of the optimal NSAID's formulation, contribute to the success of the treatment. Gel formulations represent the optimal substrate for topical NSAID's both for best penetration and for best acceptance by patients. Gel formulations of topical NSAID's represent the optimal substrate for transdermal penetration and are best accepted by patients. They are also the optimal medium for sonophoresis, which is why they can be widely used in the field of physical medicine and rehabilitation.