Traditional understanding of osteoarthritis-related pain has recently been challenged due to evidence supporting a key role of central sensitization in a subgroup of this population. This fact may lead musculoskeletal therapists to incorrectly conclude that hands-on interventions have no place in OA management, and that hands-off interventions must be applied to the exclusion of others. The objective of this paper is to encourage clinicians in finding an equilibrium between hands-on and hands-off interventions in patients with osteoarthritis-related pain dominated by central sensitization. The theoretical rationale for simultaneous application of manual therapy and pain neuroscience education is presented. Practical problems when combining these interventions are addressed as well. Future studies ought to investigate the combined effects of these treatment strategies to examine whether they increase therapeutic outcomes in comparison to current approaches for chronic osteoarthritis-related pain.