The joint is a common site of musculoskeletal infection in adults. Septic arthritis is the most serious, although not the most frequent, cause of a hot swollen joint or joints. The diagnosis rests principally on clinical suspicion. Investigation of suspected joint sepsis is urgent in order to avoid significant morbidity and mortality. This review will cover the aetiology, pathogenesis, clinical features, investigation and management of native joint sepsis in adults, and will highlight the gaps in the evidence base regarding its pharmacological management and suggest some areas for future research. It will briefly cover osteomyelitis, which is much more common in young children than it is in adults.