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For over a thousand years, various substances have been applied to the skin to treat pain. Some of these substances have active ingredients that we still use today. However, some have been discontinued due to their harmful effect, while others have been long forgotten. Recent concerns regarding the cardiovascular and renal risk from nonsteroidal anti-inflammatory drugs, and issues with opioids, have resulted in increasing demand and attention to non-systemic topical alternatives. There is increasing evidence of the efficacy and safety of topical agents in pain control. Topical analgesics are great alternatives for pain management and are an essential part of multimodal analgesia. This review aims to describe essential aspects of topical drugs that physicians should consider in their practice as part of multimodal analgesia. This review describes the mechanism of popular topical analgesics and also introduces the most recently released and experimental topical medications.