Resistance to antituberculosis drugs is due to the occurrence of resistant mutants in the bacterial population even before exposure to these drugs. These mutations are chromosomal in origin. Resistance occurs when the bacterial population is large or when drugs are used alone. Potent drugs such as rifampicin, isoniazid and streptomycin are effective in preventing emergence of resistance. Resistance to isoniazid and streptomycin was found to have minimal influence on response to short-course chemotherapy. On the other hand rifampicin resistance was associated with a high failure rate. Control of resistance is important to maintain the success of short-course chemotherapy. The restriction of the use of rifampicin to treatment of tuberculosis in combined drug regimens will reduce the occurrence of resistance to this essential drug.