Melioidosis is a tropical infection caused by the environmental bacterium, Burkholderia pseudomallei. Although this disease is endemic in Southeast Asia and northern Australia, ease of transportation promotes the distribution of disease outside the endemic regions. Patients with diabetes mellitus or chronic renal failure are particularly susceptible to this disease, increasing its global burden. This disease can be difficult to diagnose because of the diverse clinical presentations, ranging from fatal systemic illness to a chronic localized infection. The bacterium is intrinsically resistant to a wide range of antibiotics and thus requires a specific antimicrobial treatment. Appendicular musculoskeletal infections can present as either a part of multi-organ involvement or localized infection. An ineffective or inadequate course of treatment may result in a high fatality rate or recurrent disease. Delay of treatment leads to serious structural damage to various organs and long-term morbidity. The manifestations of musculoskeletal melioidosis are nonspecific, but the combination of clinical and radiological features can provide a clue to the correct diagnosis. This chapter emphasizes the role of imaging in the diagnosis and treatment of melioidosis of the appendicular skeleton.