For the last decade, high-dose intravenous ceftazidime has been the drug of choice for the treatment of severe melioidosis, after ceftazidime was shown to be superior to the 'conventional' four-drug regimen (chloramphenicol, doxycycline and trimethoprim-sulphamethoxazole) in a randomised trial. Combination ceftazidime-trimethoprim-sulphamethoxazole was compared with the conventional regimen in a separate trial with similar results, but we still do not know whether such combination therapy is needed in melioidosis. Co-amoxiclav (amoxycillin-clavulanate) has been shown to be effective but was associated with a higher rate of treatment failure than ceftazidime. Two further treatment trials in acute melioidosis have recently been conducted in Thailand. In the first of these, high-dose intravenous imipenem was compared with ceftazidime and the results suggest that the two regimens possess similar efficacy. Cefoperazone-sulbactam has been compared with ceftazidime-trimethoprim-sulphamethoxazole in a small number of patients, and further results are awaited. Relapses of melioidosis should be treated in a similar manner to primary infections.