The appropriate therapy for intestinal perforation in typhoid fever has been controversial since the late 1880s. Around the turn of the century, surgery became the established mode of therapy, with a mortality of 69% based on 166 patients in the English-language medical literature, and continued to be the preferred treatment until the advent of chloramphenicol in 1948. At this time the surgical mortality was approximately 50%. Following the recovery of a few patients with perforation treated only with antimicrobial agents (six initially, then eventually 22), nonsurgical therapy became the accepted mode of treatment. This change was never justified and this review demonstrates this. Appropriate therapy is virtually always surgical, usually consisting of simple closure and irrigation. Chloramphenicol alone is inadequate antimicrobial therapy in a patient with perforation and must be supplemented by other antimicrobials directed against enteric aerobic gram-negative bacilli and enteric anaerobes.