Melioidosis, infection with Burkholderia pseudomallei, is being recognised with increasing frequency and is probably more common than currently appreciated. Treatment recommendations are based on a series of clinical trials conducted in Thailand over the past 25 years. Treatment is usually divided into two phases: in the first, or acute phase, parenteral drugs are given for ≥10 days with the aim of preventing death from overwhelming sepsis; in the second, or eradication phase, oral drugs are given, usually to complete a total of 20 weeks, with the aim of preventing relapse. Specific treatment for individual patients needs to be tailored according to clinical manifestations and response, and there remain many unanswered questions. Some patients with very mild infections can probably be cured by oral agents alone. Ceftazidime is the mainstay of acute-phase treatment, with carbapenems reserved for severe infections or treatment failures and amoxicillin/clavulanic acid (co-amoxiclav) as second-line therapy. Trimethoprim/sulfamethoxazole (co-trimoxazole) is preferred for the eradication phase, with the alternative of co-amoxiclav. In addition, the best available supportive care is needed, along with drainage of abscesses whenever possible. Treatment for melioidosis is unaffordable for many in endemic areas of the developing world, but the relative costs have reduced over the past decade. Unfortunately there is no likelihood of any new or cheaper options becoming available in the immediate future. Recommendations for prophylaxis following exposure to B. pseudomallei have been made, but the evidence suggests that they would probably only delay rather than prevent the development of infection.