Over a six-year period, 12 patients were admitted to a Melbourne teaching hospital with mycobacterial infections of the musculoskeletal system. Four of the infections involved soft tissue and these included three atypical mycobacterial infections. The average age at diagnosis was 60 years. Five patients were born outside Australia. The predisposing factors included a past or family history of tuberculosis, pre-existing arthritis, alcoholism, earlier trauma, and membership of certain occupations. The average delay in diagnosis was four months. Treatment involved a combination of appropriate medication and surgical procedures that ranged from diagnostic aspiration to amputation. Mycobacterial infection of the musculoskeletal system, although uncommon in Australia, remains an important problem that requires continued awareness for early diagnosis.