Infections caused by gram-negative bacteria have continued to be a major problem for hospitalized patients. Malignant necrotizing otitis due to Pseudomonas aeruginosa has been encountered with increasing frequency as the number of older diabetic patients has increased. Nosocomial sinusitis and bacteremia due to Escherichia coli, Klebsiella pneumoniae, Enterobacter species, or P. aeruginosa develop in hospitalized patients. Bacteremia due to E. coli, K. pneumoniae, or P. aeruginosa often follows instrumentation of the urinary, respiratory, or gastrointestinal tracts in the hospitalized patient. Mortality still is excessively high. Infections of skin structure, particularly decubitus ulcers in debilitated, bedridden patients, are due to a mixed gram-negative and anaerobic flora; frequently, P. aeruginosa and Enterobacteriaceae resistant to many older agents are the major pathogens. Similarly, osteomyelitis in patients who have undergone previous surgical procedures is caused by various multiply resistant Enterobacteriaceae and P. aeruginosa. In all of these situations, therapy has usually included an aminoglycoside. The availability of drugs such as aztreonam, which has activity directed at aerobic gram-negative bacilli, provides an alternative approach that has proved successful and can be evaluated in more detail in the coming years.