Isoniazid preventive therapy for latent tuberculosis infection was introduced to clinical practice 38 years ago, in 1965, after a series of superb clinical trials (1) showed its efficacy in preventing tuberculosis in a wide variety of settings. Instead of hastening the decline in the incidence of tuberculosis in the United States as it was expected to do... isoniazid found itself in a 4-decade struggle for survival, from which it is now emerging. The pitfall was the almost immediate report of cases of fatal hepatotoxicity (2), a side effect not anticipated from results of the clinical trials. This ominous complication doomed isoniazid preventive therapy as it was originally intended, a curative treatment for every person in the United States with latent tuberculosis infection. What followed was a lengthy series of debates in the medical literature: Should isoniazid ever be used as preventive therapy? Who should receive it?