Three promising directions for improving care for osteoarthritis (OA) include novel education strategies to target unhelpful illness and treatment beliefs; methods to enhance the efficacy of exercise interventions; and innovative, brain-directed treatments. Here we explain that each of those three promising directions can be combined through a paradigm-shift from disease-based treatments to personalized activity self-management for patients with OA. Behavioral graded activity (BGA) accounts for the current understanding of OA and OA pain and allows a paradigm shift from a disease-based treatment to personalized activity self-management for patients with OA. To account for the implementation barriers of BGA, we propose adding pain neuroscience education to BGA (referred to as BGA+). Rather than focusing on the biomedical (and biomechanical) disease characteristics of OA, pain neuroscience education implies teaching people about the underlying biopsychosocial mechanisms of pain. To account for the lack of studies showing that BGA is “safe” with respect to disease activity and the inflammatory nature of OA patients, a trial exploring the effects of BGA+ on the markers of inflammation is needed. Such a trial could clear the path for the required paradigm shift in the management of OA (pain) and would allow workforce capacity building that de-emphasizes biomedical management for OA.