This chapter discusses the topical pain medications and their place in therapy. The ability to bypass first-pass metabolism and minimize systemic side effects allows for safer options, especially for patients on multiple medications. Topical pain medications have applications in many different disease states. They can be utilized to help manage pain symptoms or combined to offer synergistic effects. Neuropathic pain is a debilitating condition that impairs patient quality of life. Capsaicin is a lipophilic compound that diffuses poorly into aqueous solutions in the body, making it ideal for topical, localized delivery. Various pain syndromes are multi-factorial and difficult to treat. Often, a multimodal treatment approach is needed to best help the patients with these severe and refractory conditions. The evidence for the efficacy of topical pain gels is conflicting depending on the various studies cited here; however, some do show great efficacy and warrant a trial in patients who are not responding to the various modalities.