Chronic knee pain from osteoarthritis (OA) is a common cause of disability and represents, due to its constantly increasing prevalence, a huge burden on healthcare resources. The clinical presentation, however, is varied and a plethora of factors have been implicated in the onset and/or progression of the disease. Pain and physical dysfunction are the most important symptoms and they are typically monitored to evaluate the disease burden or treatment success over time. A considerable proportion of osteoarthritis patients have co-existing medical conditions that worsen the impact of osteoarthritis and can, thus, have a negative impact on the prognosis of symptoms, which deteriorate over the course of time. Evidence demonstrates that pain is a complex construct that is associated with poor quality of life, depression, disturbed sleep, functional disability, as well as reduced capacity to work. Therefore, assessing the impact of pain on the patient’s life is important as it may represent a broader concept than OA-related pain and function, one that is more representative of the biopsychosocial model.