The combination of two injectable streptogramins, quinupristin/dalfopristin, provides a new pharmacological choice proven to be therapeutically efficacious against most Gram-positive, multi-resistant microorganisms. They have been shown to be efficacious above all in critically ill patients hospitalized in intensive care who have unique alterations in homeostasis that makes tissue penetration of various pharmacological antimicrobials difficult. In cases of infection localized in difficult-to-treat sites, the combination with other drugs, such as cefepime, a glycopeptide or linezolid, is able to potentiate the action of the streptogramin with positive results which allow resolution of the illness. In this article, we review data from the literature on the use of quinupristin/dalfopristin in the treatment of Gram-positive, multi-resistant infections in critically ill patients.