Tuberculosis is an ancient disease that has accompanied humanity for the last three thousand years and is considered the oldest infectious disease that still exists. The Mycobacterium tuberculosis bacillus was spread worldwide due to human migrations, and there is archaeological evidence of spinal tuberculosis cases in Egyptian and Andean mummies, as well as texts that attributed the disease to social factors before suspecting its infectious nature. Throughout its history, humans have dealt with this pathology by developing unusual and ineffective therapies, leading to a significant increase in the disease's mortality. In the past century, the first antibiotics were introduced, bringing hope to eradicate this disease. However, evolutionary pressure has led to the emergence of multi-drug-resistant strains. Today, the development of computational techniques, such as artificial intelligence, has given us new hope for generating drugs and potential immunomodulatory therapies. However, it is essential to remember that those who do not know their history are doomed to repeat it. In this review, we summarize the history of tuberculosis, analyzing theories of its possible origin, its discovery, the creation of the first empirical treatments, vaccines, the emergence of new antibiotics, and how the mycobacterium quickly develops resistance.Licencia CC 4.0 (BY-NC-ND) © 2024 Revista Médica del Instituto Mexicano del Seguro Social.