Sulfonamides and trimethoprim are inexpensive and effective antibacterial drugs that have been used extensively. The use of sulfonamides for systemic use has, however, decreased dramatically for several years, mainly because of resistance development in pathogenic bacteria and allergic side effects. Also the clinical efficiency of trimethoprim has been severely hampered by resistance in recent years. Pathogenic bacteria show many different patterns of chromosomal resistance to sulfonamides and trimethoprim, respectively. Some of these indicate the irreversibility of resistance, since the chromosomal changes mediating resistance incur no fitness cost on the bacterium. Transferable resistance to sulfonamides and trimethoprim is mediated by plasmid-borne genes expressing resistant variations of the target enzymes dihydropteroate synthase and dihydrofolate reductase, respectively.