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Particularly in Southeast Asia drug resistance has become a major constraint in the treatment of falciparum malaria. So far relatively little is known about the current status of drug resistance in Bangladesh. The aim of this study was therefore to determine the in vitro drug susceptibility of Plasmodium falciparum in south-eastern Bangladesh. In the HRP2 in vitro drug sensitivity assay the tested isolates demonstrated a relatively high sensitivity to dihydroartemisinine (IC50 = 1.33 nM; 95% CI: 1.08-1.63; IC90 = 2.65 nM; 95% CI: 2.13-3.29), mefloquine (IC50 = 11.26 nM, 95% CI: 9.75-13.0; IC90 = 19.55 nM, 95% CI: 15.73-24.29) and quinine (IC50 = 73.24 nM, 95% CI: 65.26-82.21; IC90 = 157.75 nM, (95% CI: 134.16-185.5) thus being significantly more sensitive to mefloquine and quinine than isolates from Thailand. Chloroquine (IC50 = 93.06 nM, 95% CI: 80.38-107.76; IC90 = 214.76 nM, 95% CI: 175.64-262.62) sensitivity was highly compromised with inhibitory concentrations reaching levels comparable to Thailand. Therefore this drug should not be used in the treatment of falciparum malaria in this region. Despite compromised in vitro drug sensitivity to sulfadoxine/pyrimethamine, in clinical studies the combination of sulfadoxine (IC50 = 40.46 microM, 95% CI: 31.15-51.97; IC90 = 173.48 microM, 95% CI: 120.78-249.17) and pyrimethamine (IC50 = 1.7 microM, 95% CI: 1.25-2.3; IC90 = 4.83 microM, 95% CI: 3.17-7.37) with quinine proved to be an interesting option for treating uncomplicated falciparum malaria in Bangladesh.