Gram-positive bacteria are common causes of bloodstream and other infections in hospitalized patients in the United States, and the percentage of nosocomial bloodstream infections caused by antibiotic-resistant gram-positive bacteria is increasing. Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) are of particular concern. In the United States, approximately 60% of staphylococcal infections in the intensive care unit are now caused by MRSA, and percentages continue to rise. Outbreaks of hospital-acquired MRSA (HA-MRSA) are typically the result of clonal spread by MRSA being transferred from patient to patient, frequently using healthcare personnel as intermediaries. HA-MRSA strains are generally multidrug resistant. Vancomycin is the standard treatment for serious MRSA infections, but a few cases of vancomycin-resistant S aureus (VRSA) have recently emerged in the United States. Community-acquired MRSA (CA-MRSA) is also increasing. Soft tissue infections are the most frequent presentations of CA-MRSA, but life-threatening invasive infections occur as well, including necrotizing pneumonia. The mechanisms of methicillin resistance are the same for CA-MRSA and HA-MRSA, but susceptibilities to non-â-lactam antibiotics often differ. CA-MRSA exhibits broader antibiotic susceptibility than does HA-MRSA. The proportion of enterococci resistant to vancomycin continues to rise in the hospital setting, with the overwhelming majority of infections due to Enterococcus faecium. Clonal spread of VRE has been documented, but polyclonal outbreaks associated with antimicrobial use are also common. The relations between antibiotic use and VRE colonization are complex and related to the antienterococcal activity, biliary excretion, and antianaerobic activity of the antibiotic. Recent results show a decline in invasive pneumococcal disease (IPD) since the introduction of 7-valent pneumococcal conjugate vaccine, and suggest that, where available, vaccines may be useful in the battle to slow the spread of resistant gram-positive cocci.