The incidence of multiresistance in Gram-positive cocci causing infections in critically ill patients admitted to the intensive care unit (ICU) has increased notably in recent years. Thus, therapeutic proposals have been modified according to the emergence of multiresistant cocci and adapted to epidemiological markers of individual infectious processes, geographical variations of these markers, the availability of new antibacterials, and advances in the knowledge of pharmacokinetic and pharmacodynamic aspects of their use. The current management of critically ill patients should consider new therapeutic approaches, such as the "de-escalating strategy", which includes the administration of empirical antibacterials active against multiresistant pathogens followed by directed treatment based on unequivocal data from antibacterial-susceptibility testing. Optimisation of antibacterial treatment should be viewed in the context of the need to determine plasma drug concentrations, pharmacoeconomic considerations and control of drug-related adverse events. Therapeutic proposals should be developed within the framework of the antibacterial policy of each hospital. The present review is focused on the description of the therapeutic strategies for the main infectious processes caused by Gram-positive cocci in severely ill patients admitted to the ICU according to a review of the pertinent literature and the clinical experience of the authors.