Nosocomial bloodstream infections (BSIs) have become an important cause of morbidity and mortality, particularly in intensive care units (ICUs). Gram-positive organisms are the prevalent causes of antibiotic-resistant BSI, especially Staphylococcus aureus, coagulase-negative staphylococci and enterococci. In recent years, several reports have shown an increase in antimicrobial resistance among Gram-positive bacteria isolated from patients in ICUs. In this context, methicillin-resistant Staphylococcus aureus (MRSA) is a major problem. In the ICU more than 50% of S. aureus isolates in Europe are resistant to methicillin. Although vancomycin became the drug of choice for MRSA and is still widely used for this indication, many studies suggest that when vancomycin MIC values are at the high end of the susceptibility range, vancomycin is less effective against MRSA. High MRSA prevalence combined with the widespread use of vancomycin for empirical Gram-positive coverage may lead to changes in patient outcomes. Here we describe the microbiological, pharmacological and clinical characteristics of three new antibacterials helpful in severe infections in ICU patients: linezolid, tigecycline and daptomycin. These new drugs have some limitations, and the possibility developing resistance is real. Knowledge of both old and new antibacterials is necessary to utilize them most effectively.