A decade ago, the nosology of bacterial skin and soft tissue infections appeared to be well understood, and their treatment appeared established and effective. During the intervening period, numerous changes have occurred, renewing the challenge of diagnosis and treatment of these infections. A number of social changes as well as the emergence of new pathogens have altered that rather simplistic view. For numerous reasons, several million citizens of the United States are homeless and lack access to facilities fulfilling basic human needs, including health care. The human immunodeficiency virus epidemic is expanding at an uncontrolled rate in all geographic regions; those infected are at risk for more frequent and more severe bacterial infections. Linked with the human immunodeficiency virus epidemic and the problem of homelessness is an increase in the number of cases of tuberculosis. New bacterial pathogens continue to be identified, and the role for known pathogens is expanding,eg, Vibrio vulnificus. Group A β-hemolyticStreptococcus pyogenesis being reported to cause infections with greater morbidity and mortality. Lyme borreliosis is gradually spreading to involve all the continental United States, with approximately 10,000 cases reported in 1991.