Mupirocin inhibits the activity of bacterial isoleucyl-tRNA synthetase resulting in a decrease or cessation of protein synthesis. Expression of resistance in staphylococci has been divided arbitrarily into two groups, low level (minimum inhibitory concentrations [MIC] of between 8 and 256 mg/L) and high level (MICs of > or = 512 mg/L). Low level resistance is associated with spontaneous mutational events, while high level resistance is mediated by a large transferable plasmid. The introduction of a nasal formulation of mupirocin raises many issues concerning staphylococcal breakpoints, since 20,000 mg/L is applied to the mucosal surface to eradicate nasal colonisation with staphylococci, as opposed to eliminating infection. For several years after its introduction reports of resistance in staphylococci were rare. However, the contemporary literature indicates reports of resistance in select populations, particularly associated with dermatology patients. The overall rate of resistance for organisms isolated from the nares is currently unknown. The recent introduction of the E test combined with the 5 microgram screening disk may assist in determining resistance rates in large populations.