The reported incidence of Salmonella infections in the United States has increased substantially since reporting began in 1943. These infections cause important morbidity, mortality, and economic burden in this country and are particularly severe in the infant, elderly, or immunocompromised patient. Four recent trends suggest that salmonellosis will present an increasing challenge to public health in the future. Antimicrobial resistance is present in an increasing proportion of Salmonella isolates. Salmonella bacteremia has emerged as a serious complication of human immunodeficiency virus infection. Infections caused by the egg-associated serotype Salmonella enteritidis are steadily increasing in incidence and geographic scope, and these infections are now the most common form of salmonellosis in some parts of the country. Finally, contamination of food produced in centralized facilities has led to extremely large and widespread outbreaks. Better understanding of the biology of specific animal reservoirs and of the microbiologic aspects of food processing is needed to control salmonellosis in the future.