The most common disabling symptom of osteoarthritis (OA) is pain. Clinical investigations using disease-specific animal models have increased our insights into the pathophysiology of osteoarthritic pain. As the prevalence of OA continues to rise and current available treatment options give less than optimal levels of pain relief, opportunities to develop treatments to address osteoarthritic pain are increasing. Targeted administration of local anesthetics along sensory/motor nerves can provide an alternative strategy for managing osteoarthritic pain. Moreover, the development of engineered therapeutic drug delivery systems may allow for sustained perineural delivery of local anesthetics as opposed to the traditional intraarticular joint injections. This review presents an overview of 1) the pathophysiology of persistent pain associated with OA of the hip, shoulder, and knee and 2) the emerging therapeutic role of local anesthetics in providing analgesia for joint-related pain symptoms.