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Tuberculosis reactivation causes significant morbidity and mortality especially in immunocompromised patients such as solid organ transplant (SOT) recipients. Therefore, treating latent tuberculosis infection (LTBI) is critical. The treatment of LTBI with former first line regimen, isoniazid monotherapy for 9 months, can be challenging, as it is associated with higher toxicity risk and lower treatment completion rates. Isoniazid monotherapy for 9 months is more likely to cause liver toxicity compared to other regimens and its rate of completion can be lower than 50%.  As of result of this, there has been a shift in the treatment of LTBI. The following short-regimens: 3 months of weekly isoniazid plus rifapentine, 4 months of daily rifampin and 3 months of daily isoniazid plus rifampin, have replaced 9-month isoniazid monotherapy as first line treatments for LTBI, after the new guidelines of LTBI management were published in 2020 by the Centers for Disease Control and Prevention (CDC) and National Tuberculosis Controllers Association. These short regimens for LTBI are effective and safe in SOT candidates. However, close monitoring for drug-drug interactions are paramount.