Gram-positive cocci, in particular Staphylococcus aureus, account for as much as one-third of all cases of hospital-acquired pneumonia, and treatment has become increasingly complex as the proportion of resistant isolates has increased. Methicillin-resistant S. aureus is of particular concern because this pathogen is now associated with hospital-acquired, ventilator-associated, community-acquired, and healthcare-associated pneumonia. Antibiotic therapy for ventilator-associated pneumonia is challenging because it can be caused by multiple pathogens, which can be resistant to multiple drugs. This article reviews the epidemiology of ventilator-associated pneumonia and describes options for antibiotic treatment. Particular attention is paid to pneumonia due to methicillin-resistant S. aureus. Studies suggest that vancomycin, the traditional treatment for ventilator-associated pneumonia, may not be the best option for this type of pneumonia and that other antibiotics, such as linezolid and clindamycin, might be better choices. New antibiotics with activity against methicillin-resistant S. aureus are under investigation and may soon become available for clinical use. Studies are needed to define the optimal choice of antibiotic for pneumonias caused by this organism, and these choices will need to be balanced with the need to minimize the emergence of resistance.