In this article, we present the case for the existence of a subgroup of patients with osteoarthritis (OA) who experience pain with neuropathic features. Recognizing these patients as a distinct subgroup will allow clinicians to improve the management of their symptoms. We discuss the diagnostic criteria for pain to be classed as neuropathic, then systematically examine the applicability of these criteria to the symptoms, signs and pathology of OA. What are the implications for the preclinical development and clinical use of analgesics for OA? How should existing treatment options be reassessed? Differences in the aetiology of OA and the pharmacological sensitivity of patients with OA pain with neuropathic features, compared with other patients with OA, might explain the frequent negative findings of clinical trials of treatments for symptomatic OA. If the global prevalence of OA pain with neuropathic features is accurately represented by reports from small experimental groups of patients, then a substantial unmet need to tailor diagnosis and therapy for these individuals exists.