Musculoskeletal pain is one of the most common concerns and chief complaints of patients worldwide. Pharmacological intervention is often an important part of the multimodal approach to managing this painful condition. Musculoskeletal pain is primarily somatic and nociceptive in nature, but can often include neuropathic components. Simple analgesics including acetaminophen and nonsteroidal anti-inflammatory drug (NSAIDs) are often first-line treatments. Additional adjuncts include muscle relaxants and neuropathic agents such as gabapentinoids and antidepressants. Opioids are another class of medications used for the treatment of musculoskeletal pain; however, their use is controversial due to insufficient evidence of long-term efficacy and the risk of harm.