The microbial aetiology of large joint sepsis is changing now that joint replacement therapy is becoming common place. The clinical history and examination may give important clues about the likelihood of infection and the possible involvement of unusual organisms. Newly introduced technology to improve the sensitivity of tests for the presence of micro-organisms in synovial fluid has not yet made a significant contribution to routine management. New imaging techniques such as magnetic resonance imaging are likely to improve patient management, but their utility is still under assessment. Arthroscopic biopsy to obtain material for culture and histology is particularly important in suspected chronic septic arthritis. Prosthetic joint infections present a particular challenge to microbiologists since the organisms involved are often found in small numbers and are common skin contaminants. Optimal microbiological management involves the taking of multiple (> or = 5) samples, careful processing to resuscitate organisms whilst avoiding contamination, and careful interpretation of results in the light of the clinical and histological picture.