There has been a significant increase in the number of bacteremias sustained by hospitalized patients over the past 45 years. Responsible bacterial flora has shifted from streptococcal to staphylococcal to gram-negative. Simultaneously, the patient population has become significantly older. Two types of nosocomial infection are reviewed in this clinical setting. Pneumococcal disease still accounts for 10% of nosocomial pneumonias and 5-10% of nosocomial bacteremias. Antimicrobial therapy, although effective, has not eliminated mortality, particularly among older patients with one or more underlying diseases. Vaccination with pneumonococcal polysaccharide vaccine may reduce the morbidity and mortality associated with this infectious process. Several Pseudomonas vaccines have been evaluated, but none has proven both efficacious and non-toxic. Further development of a gram-negative vaccine, preferably one which protects against several types of bacteria, is required.