Pneumonia is the second most common type of nosocomial infection and is most prevalent in patients who are mechanically ventilated. Nosocomial pneumonia (NP) is the leading contributor to mortality in patients, accounting for approximately 50% of deaths in patients with hospital-acquired infections. Several factors place patients at risk for developing NP, including prolonged length of hospital stay and local epidemiology. Gram-positive pathogens such as Streptococcus pneumoniae and, more recently, Staphylococcus aureus, as well as atypical organisms such as Legionella spp are increasingly associated with NP. Emerging antimicrobial resistance among these organisms confounds treatment interventions. Lack of local definitive information and patient comorbidities further complicate the physician's treatment decisions. The role of invasive pulmonary diagnostic techniques remains problematic and controversial. Studies, however, have shown that early initiation of appropriate empiric therapy is essential to improving patient outcome and reducing mortality. This article will review therapeutic options and appropriate antimicrobial agents for use in the treatment of nosocomial pneumonia in the era of emerging drug resistances.