Control of the TB pandemic is unlikely without a vaccine that effectively prevents clinical TB in adolescents and adults. Within a relatively sparse pipeline of novel TB vaccines in clinical trials, the most advanced candidate is M72/AS01E-4, which contains 2 Mycobacterium tuberculosis (Mtb) proteins and the adjuvant AS01E-4. The vaccine has demonstrated 50% efficacy in preventing clinical TB in adults in a phase 2b trial and is now being tested in a 20,000-person phase 3 trial. The fast-following candidate MTBVAC is a live attenuated strain of Mtb and is now entering phase 2b testing. Multiple other novel candidates are in phase 1, 2, and 3 trials. These include “next-generation” vaccines such as the subunit vaccines H107/CAF10b and ID93/GLA-SE and the mRNA vaccines BNT164a1 and BNT164b1, which incorporate more rational antigen selection and adjuvant capacity based on recent advances in understanding protective immunity against Mtb.