The emergence of multiresistant bacterial strains and the continuing burden of infectious disease globally point to the urgent need for novel affordable antimicrobial drugs. Thioridazine is a phenothiazine antipsychotic drug with well-recognized antimicrobial activity, but this property has not been harnessed for clinical use as a result of its central nervous system and cardiac side-effects. The cardiotoxicity of thioridazine has recently been shown to be structurally specific at a molecular level, whereas its antimicrobial properties are shared by a number of phenothiazine analogues. This raises the possibility that its enantiomers or its inactive metabolite, the ring sulphoxide, may act as a lead compound in the future development of antimicrobial drugs to face the new challenges in infectious disease.