Total knee replacement (TKR) is considered an effective intervention for the treatment of chronic knee pain and disability. Yet there is increasing evidence, based on research using patient-based outcome measures, that a significant proportion of patients experience chronic knee pain, functional disability, a poor quality of life and dissatisfaction after TKR. Although some poor outcomes after TKR are due to surgical technique and implant factors, much of the pain and disability after surgery is medically unexplained. A range of possible patient factors could contribute to a poor outcome after TKR. Socio-demographic factors that have been found to correlate with a poor outcome after TKR include female gender, older age and low socio-economical status. Medical factors that are highly predictive of pain and disability after TKR are a greater number of co-morbidities and a worse pre-operative status. A range of psychological factors could be predictive of a poor outcome after surgery including depression, low self-efficacy, poor pain coping strategies, somatization, low social support and patient expectations. It is also proposed that a biological explanation for continuing pain after TKR could involve central sensitisation, a dysfunction of pain modulation by the central nervous system. To improve patient selection for TKR, future research needs to focus on developing a pre-operative screening protocol to identify those patients at risk of medically unexplained pain and disability after TKR.