Hospital-acquired pneumonia accounts for significant morbidity and mortality in hospitalized patients. Gram-negative bacilli and Staphylococcus aureus are the most common isolates in these patients. Since the etiology of the disease is usually unknown, empirical broad-spectrum antibiotic therapy is given based on the severity of illness, time of onset, specific risk factors and local prevalence of pathogens. Treatment with a single broad-spectrum antibiotic agent (third-generation of cephalosporins, carbapenemes and fluoroquinolons) is recommended in the absence of specific risk factors and Pseudomonas aeruginosa. Combination treatment modalities with beta-lactam antibiotics and aminoglycosides is still the cornerstone of empirical antibiotic treatment of severe hospital-acquired pneumonia.