Pakistan has a population approximately 136 million people, of which 67 are under 18 years of age. Infectious diseases account for the majority of the 5 million deaths annually in children under 5 years of age. with diarrhea and acute respiratory ilnesses as the major killers. Typhoid fever is however a major cause of morbidity among the urban and peri-urban population, and although accurate community-based prevalence data is unavailable, it is estimated that the annual incidence of typhoid in Karachi is about 500 cases per 100,000 population. Although isolated cases of chloramphenicol resistance have been known for a long time, the mid 1980s saw the emergence of strains of Salmonella typhi to all the three primary oral antibiotics. These multi-drug resistant (MDR) strains initially accounted for 10-15% of all isolates but rose to almost 50% of of all cases of typhoid by 1994/1995, placing an enormous burden on already strained health resources. Although typhoid cases in infancy account for only 15% of all children, the morbidity and mortality is considerably greater, representing both atypical presentation as well as a greater severity of the disorder in younger infants. Although there are encouraging trends of a reduction in the relative proportion of MDR strains of typhoid in 1996, they still account for 38% of all paediatric Salmonella typhi isolates. Given the limited resources available for cases management, appropriate antimicrobial therapy of MDR typhoid has posed particular problems in Pakistan. Although i.v ceftriaxone was shown to be effective in the therapy of MDR typhoid, it is prohibitively expensive and in contrast to infection with sensitive strains of typhoid, therapy for greater than 7 days is required Therapy with oral quinolones has posed problem in recent years with emergence of resistant strains. It is imperative therefore that the focus clearly remain on preventive strategies for typhoid.