The antimicrobial activity of synthetic, non-chemotherapeutic compounds, such as the phenothiazine, methylene blue, has been known since the time of Ehrlich (1854-1915). In this context the term 'non-antibiotics' is taken to include a variety of compounds which are employed in the management of pathological conditions of a non-infectious aetiology, but which modify cell permeability and have been shown to exhibit broad-spectrum antimicrobial activity. The antimicrobial properties of compounds such as phenothiazines, as well as those of other neurotropic compounds, have only been investigated sporadically, and their application to management of microbial infections has not been evaluated. A review of the literature, coupled with a number of more recent investigations, suggests that some of these and other membrane-active compounds enhance the activity of conventional antibiotics, eliminate natural resistance to specific antibiotics (reversal of resistance) and exhibit strong activity against multi-drug resistant forms of Mycobacterium tuberculosis. Thus non-antibiotics may have a significant role in the management of certain bacterial infections.