In addition to their impressive, well-publicized and well-researched propensity to evolve and acquire genetically determined mechanisms for resistance to antibiotics, bacteria that are inherently susceptible to these drugs can also be phenotypically refractory to their action. This phenomenon of 'non-inherited resistance' to antibiotics has been known since the beginning of the antibiotic era but, relative to inherited resistance, it has been given little attention. Here, we review the in vitro and in vivo evidence for the different forms of non-inherited resistance and the mechanisms responsible. With the aid of a simple mathematical model and computer simulations, we show how non-inherited resistance could extend the duration of antibiotic treatment, cause treatment failure and promote the generation and ascent of inherited resistance in treated patients.