Bacterial persistence is the capability of microorganisms to survive in the host despite adequate antimicrobial treatment. This is a general phenomenon and has been observed during infection with a number of organisms. The subject is reviewed in relation to the treatment of leprosy. The presence of persisters in the large bacterial populations that exist in patients with lepromatous leprosy is not surprising. It is unlikely that in the near future a new drug or combination of drugs will be found that is capable of eradicating persisting M. leprae. It may be useful, nevertheless, to reconsider whether the sporadic demonstration of viable, drug-susceptible organisms after antimicrobial treatment of variable duration and efficacy warrants a policy of life long chemotherapy in lepromatous leprosy.