The epidemiology of nosocomial and community-acquired infections has changed in recent years. Methicillin-resistant Staphylococcus aureus (MRSA), especially community-associated MRSA (CA-MRSA), has emerged as a gram-positive organism with an increasing impact in clinical practice. Infections with Acinetobacter baumannii have become a major cause of morbidity and mortality. Minocycline has significant in vitro activity against MRSA and A. baumannii that is comparable with agents currently used against these organisms. The absence of an intravenous (i.v.) minocycline formulation in recent years has limited its use in seriously ill patients infected with these organisms. However, minocycline i.v. has recently been reintroduced to the US market. The objective of this study was to review available information on the chemistry, mechanism of action, in vitro activity, resistance mechanisms, pharmacokinetics, tolerability and efficacy of minocycline against MRSA and A. baumannii. This article provides suggestions for future studies and potential uses of minocycline and is designed to trigger interest in systematic clinical evaluation of minocycline for patients infected with these organisms. In conclusion, minocycline is an old drug that has the potential to become an important part of the armamentarium against emerging infections such as CA-MRSA and A. baumannii. Owing to its promising profile against these clinically important pathogens as well as excellent pharmacokinetic properties, minocycline merits evaluation in serious infections.