Melioidosis is caused by Burkholderia pseudomallei, a Gram-negative environmental saprophyte found in tropical and subtropical regions globally. The aims of treatment for melioidosis are to prevent death and other complications of septic shock, and to eradicate B. pseudomallei and prevent relapse. To achieve these aims, treatment comprises an intensive phase involving minimum 10-14 days of intravenous ceftazidime, meropenem, or imipenem, and a prolonged eradication phase of at least 3 months of oral trimethoprim-sulfamethoxazole. Here, we review the clinical trial and other evidence that supports melioidosis treatment guidelines, and the approach to complications including treatment side effects, relapse, and antimicrobial resistance.