Chronic pain is a complex disorder with multiple etiologies for which the pathologic mechanisms are still largely unknown, making effective treatment a difficult clinical task. Achieving pain relief along with improved function and quality of life is the primary goal of pain clinicians; however, most patients and healthcare professionals consider 30% pain improvement to be clinically significant-a success level that would be unacceptable in other areas of medicine. Furthermore, patients with chronic pain frequently have multiple comorbidities, including depression and sleep apnea, and most have seen several physicians prior to being seen by a pain specialist, have more than three specific pain generators, and are taking multiple medications. The addition of further oral medications to control pain increases the risk of drug-drug interactions and side effects. However, topical analgesics have the advantage of local application with limited systemic levels of drug. Topical therapies benefit from reduced side effects, lower risk of drug-drug interactions, better patient acceptability/compliance, and improved tolerability. This two-part paper is a review of topical analgesics and their potential role in the treatment of chronic pain.