Shigellosis is an important cause of infectious diarrhea in Vietnam, caused mainly by Shigella flexneri. This study provides for the first time in the international literature, data on the development of antimicrobial resistance in Shigella between 1988 to 1998, including data reported to the National Program for Surveillance of Antimicrobial Resistance (NPSAR). Our studies show that about 80% of the Shigella strains tested were resistant to ampicillin, chloramphenicol, oxytetracycline, trimethoprim and sulfonamides. This combination of drugs was also the most common antibiogram among multiple-resistant S. flexneri (57%). Resistance to tetracyclines, sulfonamides and, in particular trimethoprim (p<0.001), increased during the study period. Our findings indicate that tetracyclines and co-trimoxazole (a combination of a sulfonamide and trimethoprim), which are recommended and commonly used drugs for the treatment of shigellosis in Vietnam, may have limited therapeutic effect. In contrast to neighboring countries, low percentages of resistance were found to nalidixic acid and norfloxacin (3-5%) and no resistance was found to ciprofloxacin, indicating that nalidixic acid with its low cost and safety in children could be recommended for the treatment of shigellosis. The NPSAR provides a useful picture of the levels and development of antimicrobial resistance in Vietnam and should receive continued support for further improvement by increasing the number of provinces covered, the numbers of isolates tested from rural areas, and the communication of results to medical practitioners and others prescribing and/or selling antimicrobials.