This study aims to educate medical practitioners on possible synovial disoders that may be the cause of persistent knee pain and recurrent effusions. Histopathological audit of arthroscopic synovial biopsies done for persistent knee effusions. Monoarticular knee pain and swelling has a plethora of differential diagnoses. In South Africa tuberculosis is a common treatable cause that needs to be excluded. The presence of multiple comorbidities and unremarkable septic markers may pose a diagnostic challenge. This necessitates the need for synovial biopsy. We review the clinical presentation and histopathological diagnoses of patients who had arthroscopic knee synovial biopsies for persistent undiagnosed knee effusions. A retrospective review of patients who had knee arthroscopy was done. Those who had diagnostic arthroscopy and synovial biopsy done were included in the study. Comorbidities, blood results (white cell count, C-reactive protein and erythrocyte sedimentation rate) and histopathological diagnoses were recorded. Descriptive statistical analysis of continuous and categorical variables was perfomed. Out of 194 arthroscopies, 19 patients had biopsy done. Only 10 histopathology results were found. Mean age was 40.6 SD 10.3 years (range 24-55 years). All cases presented with knee effusion and pain. Duration of symptoms ranged from 1-8years with a median of 3.25 years (IQR 1.25-6.5). Two patients were documented HIV positive with one having co-existing systemic lupus erythematosus. One had previous tuberculosis treatment and there was one rheumatoid arthritis patient on treatment. Mean white cell count was 6.13x10?/L (SD 1.57x10?) with range 4.56-8.60x10?. Median ESR was 17mm/hr (IQR 15-19) and CRP range was 3-20mg/L. Histopathology revealed 3 cases of pigmented villonodular synovitis (30%), 2 cases of synovial lipomatosis (20%) and 1 each of mycobacterium tuberculosis, rheumatoid arthritis, connective tissue disease, chronic synovitis and combined necrotising and non-necrotising granulomatous inflammation. Diagnostic arthroscopies are overshadowed by the need for therapeutic intervention for ligament or meniscal repair. However it has a role in clinching a diagnosis in cases of long standing knee effusions that pose a diagnostic dilemma. The majority of patients had biopsy done mainly to rule out tuberculous infection. These were patients with persistent knee pain and effusions despite treatment with DMARDs in the setting of coexistent immunosuppression. This study reveals a wide range of synovial disorders that may be the underlying cause of chronic knee pain and effusions. PVNS and synovial lipomatosis were the leading histopathological diagnoses. Arthroscopic synovial biopsy is reliable in reaching a histopathological diagnosis in cases of persistent undiagnosed painful knee effusions.