Eradication of tuberculosis seems to be a long way off especially with the growing of drug resistance tuberculosis and HIV co-infection tuberculosis. The gaps in our knowledge and the limited sensitive and specific biomarkers especially for latent tuberculosis infection make it defensive. The fate of tuberculosis treatment ranged from cured to failure and there are many risk factors involved apart from the immune state and age. Therefore, this review focuses on the understanding of tuberculosis disease progression and the associated risk factors of the events in the disease progression. This article also highlights the diagnostic and predictive marker that may predict the disease progression. In addition, this review highlights the potential use of rifabutin in tuberculosis treatment regimen. It is hoped that this review could give an overview on future directions of research in tuberculosis.