Typhoid fever still poses a tremendous problem in developing countries, with almost 17 million cases annually with 0.6 million deaths. Of these almost 75-80% of the cases and deaths occur in Asia alone, where the disease is endemic. Although chloramphenicol resistance has been recognized since the early 1970s, definitive reports of emergence of strains o/Salmoneila typhi resistant to ampicillin, chloramphenicol and trimethoprim-sulfa i.e. multidrug-resistant (MDR) typhoid, first appeared in 1987 from the Indian subcontinent. Since then, MDR typhoid has been reported from other parts of Asia, including the Middle East and South East Asia. These MDR S.typhi isolates have been responsible for several outbreaks against a background of endemic typhoid because of the increasing ease of international travel, MDR typhoidal isolates have also been reported from Europe and North America. Much of this resistance is known to be mediated by relatively large plasmids belonging to the HI incompatibility group among of strains belonging to the VI phage types El, Ml, CI, 05-1 and Dl-N. Limited amount of data on molecular characterization of S.typhi strains from Papua New Guinea indicate limited genetic diversity with most isolates from fatal cases possessing the pulsed-field gel electrophoresis pattern combination X1SJA1. Estimates of the relative proportion of MDR S.typhi isolates from the Indian subcontinent in recent years have ranged from 50-65%, posing considerable problems in therapy. A wide variety of therapeutic approaches have been tried, including oral guinolones and third generation cephalosporins. A worrying trend has been the recent emergence of S.typhi strains with chromosomal resistance to guinolones, along with increasing report of delayed effervescence and treatment failure. A welcome trend are the very recent report from Pakistan and India indicating a resurgence of chloramphenicol-sensitive S. typhi strains. However, these data further highlight the importance of preventive measure in typhoid control including close attention to public hygiene, food preparation, regulation of antibiotic use and vaccination strategies.