 Despite ongoing efforts to eradicate it, tuberculosis, TB, remains a global health burden that disproportionately affects poorer nations. The BCG vaccine, the only approved vaccine for TB, has been controversial due to its efficacy ranging from 0 to 80%. However, recent discoveries suggest that the vaccine provides protection against both TB and non-TB pathogens through a new immune system called trained immunity. Additionally, the vaccine's effectiveness is tied to its effect on granular sites at the epigenetic and hematopoietic stem cell levels. Different strains of the BCG vaccine elicit different immune responses, with some being more immunogenic than others. The current vaccine is being reformulated to be more effective, and next generation vaccines against TB are being developed. This article was authored by Thomas Cho, Christopher Kachadudurian, Huynu Yen, and others.