Early knee osteoarthritis poses a therapeutic dilemma to the musculoskeletal clinician. Despite the recent interest in arthroscopic and injectable regenerative therapies intended to repair or restore a focal target such as cartilage, meniscus, or subchondral bone, none have been shown to slow disease progression. A likely cause of these disappointing treatment outcomes is the failure to address chronic and excessive loading of the knee joint. A growing body of evidence suggests that first-line therapies for early knee osteoarthritis should emphasize unloading the knee joint since any potential therapeutic benefit of regenerative therapies will likely be attenuated by excessive mechanical demand at the knee joint. Minimally invasive medical devices such as patient-specific interpositional implants and extracapsular joint unloading implants are currently in development to address this clinical need.