Pain and inflammation affect patients both acutely and chronically across all patient demographics. Often, the medications which are used to target musculoskeletal conditions are poorly tolerated due to various contraindications, drug interactions, and troublesome adverse events. The investigation and development of localized, externally applied NSAIDs is on the rise among researchers and pharmaceutical manufacturers, but research is still inefficient in determining the role in therapy of transdermal analgesics and anti inflammatories. Compounding Pharmacies and FDA 503b Outsourcing Facilities aid in this critical endeavor through endogenous compounding and manufacturing (respectively) of transdermal analgesic formulations. This review summarizes the currently available data supporting the implementation of transdermal ketoprofen preparations in the management of musculoskeletal pain and inflammation. Externally applied NSAIDs are crucial in the development of pain management modalities which reduce the risk of numerous complications, including drug-drug interactions, conflicting comorbidities, and harmful systemic adverse events.