Most cases of typhoid fever in the United States occur in international travelers, with the greatest risk associated with travel to Peru, India, Pakistan, and Chile. Laboratory workers and household contacts of long-term carriers are also at greater risk than the general population. Decisions to the use typhoid vaccine involve weighing the risk of illness against the risk of vaccine reactions. Until recently, the only typhoid vaccine commercially available to US civilians was a heat-phenol-inactivated parenteral product that is 51% to 77% effective in preventing typhoid fever but frequently produces local pain and swelling, fever, headache, and malaise. A new orally administered, live-attenuated vaccine, made from the Ty21a strain of Salmonella typhi, has been recently licensed in the United States. This vaccine provides equivalent protection with a much lower incidence of adverse reactions. It is administered in a four-dose series given over 7 days. Since neither vaccine offers total protection, the most important elements in prevention of typhoid fever remain sound biosafety precautions in laboratory workers and care in selecting food and beverages by those traveling to areas where typhoid fever is endemic.