Typhoid fever, caused by Salmonella enterica seroptype Typhi (S typhi), has an estimated worldwide prevalence of 12-33 million cases. The pathogenesis of this disease depends on the ingested inoculum size of S typhi, the virulence of the strain, the host's immune response and previous exposure, and local protective factors. Numerous extra-intestinal complications can occur with S typhi infection, including the involvement of the central nervous system (3-35%), cardiovascular system (1-5%), pulmonary system (1-86%), bone and joints (< or =1%), hepatobiliary system (1-26%), genitourinary system (<1%), and others. Due to an increase in multidrug-resistant S typhi, fluoroquinolones and third-generation cephalosporins have been increasingly used for typhoid fever and its complications. We describe the epidemiology, clinical manifestations, pathogenesis, and treatment of extra-intestinal S typhi infections.