Borderline oxacillin-resistant Staphylococcus aureus (BORSA) represents a quite poorly understood and inadequately defined phenotype of methicillin resistance. BORSA strains show low, borderline resistance to penicillinase-resistant penicillins (PRPs), with oxacillin MICs typically equal to 1–8 µg ml−1, and in contrast to methicillin-resistant S. aureus (MRSA), do not have an altered penicillin-binding protein, PBP2a, encoded by the mecA or mecC gene. Their resistance is typically associated with hyperproduction of beta-lactamases or, in some cases, point mutations in PBP genes. BORSA cannot be classified as either truly methicillin-resistant or truly methicillin-susceptible strains. However, they are frequently misidentified, which poses an obvious epidemiological and therapeutic threat. BORSA strains are commonly isolated from humans and animals, and are found both in hospitals and in a community setting. The epidemiology and clinical presentation of BORSA infections seem to be similar to those for MRSA; these infections are usually more severe than those caused by methicillin-sensitive S. aureus (MSSA). Treatment of severe infections caused by BORSA may be ineffective, even with larger doses of oxacillin. The available evidence suggests that BORSA represent a frequently neglected problem, and their emergence in new environments implies that they need to be monitored and accurately distinguished from MSSA and MRSA.