It is obvious from the studies cited above, as well as many other experiences, that a range of strategies is needed to improve compliance with or adherence to programs of treatment for latent infection with tuberculosis. In addition to providing incentives and social support to improve adherence, shortening the duration of therapy might also be of great benefit. Most patients in the United States who are treated for latent infection receive either 9 months or 6 months of daily self-administered isoniazid, with 9 months being the preferred regimen for most patients, in accordance with the most recent ATS/CDC guidelines that stress again the improved efficacy of prolonged treatment. However, in the last few years, a number of studies11–12 have examined the potential role of much shorter regimens, some of which consisted of 2 months of rifampin and pyrazinamide (2RZ), which can be administered either daily or intermittently for treatment of latent infection. Randomized, controlled studies of this regimen in patients with HIV infection and positive tuberculin skin test results indicated that it is comparable in efficacy to isoniazid administered daily for 6 to 12 months.12–13 Additionally, the studies generally demonstrated higher treatment completion rates for patients on the shorter regimens. In the largest of these studies,11 adverse events were no more likely to be seen with one regimen than the other, although patients were more likely to discontinue rifampin/pyrazinamide than isoniazid. Based on these studies, the ATS/CDC guidelines recommended 2RZ as the preferred regimen in patients with HIV infection and as a suitable and effective regimen in HIV-negative persons. However soon after these recommendations were made, several deaths were reported in patients who received 2RZ.14 Although it is likely that 2RZ can be used safely in many situations, the reports of deaths associated with this regimen have certainly dampened enthusiasm for its widespread use, and it is unlikely that this regimen will come into common use in most settings.