OBJECTIVES: To systematically summarise the literature on 1) the course of pain in patients with knee OA; 2) prognostic factors that predict deterioration of pain; 3) the course of physical functioning; and 4) prognostic factors that predict deterioration of physical functioning in persons with knee OA. METHODS: A search was conducted in PubMed, CINAHL, Embase, Psych-INFO, and SPORTDiscus up to January 2014. A meta-analysis and a qualitative data synthesis were performed. RESULTS: Of the 58 studies included, 39 were of high quality. High heterogeneity across studies (I(2) > 90%) and within study populations (reflected by large standard deviations of change scores) was found. Therefore, the course of pain and physical functioning was interpreted to be indistinct. We found strong evidence for a number of prognostic factors predicting deterioration in pain (e.g. higher knee pain at baseline, bilateral knee symptoms and depressive symptoms). We also found strong evidence for a number of prognostic factors predicting deterioration in physical functioning (e.g. worsening in radiographic osteoarthritis, worsening of knee pain, lower knee extension strength, lower walking speed and higher comorbidity count). CONCLUSION: Because of high heterogeneity across studies and within study populations, no conclusions can be drawn with regard to the course of pain and physical functioning. These findings support current research efforts to define subgroups or phenotypes within knee osteoarthritis populations. Strong evidence was found for knee characteristics, clinical factors, and psychosocial factors as prognostics of deterioration of pain and physical functioning. This article is protected by copyright. All rights reserved.