Mycobacterium tuberculosis (Mtb) causes tuberculosis (TB), a debilitating disease that causes over 1.5 million deaths each year, more than any other infectious disease such as HIV, malaria, or cholera. The currently available antibiotics against Mtb require a lengthy treatment time of up to nine months and frequently the pathogen develops resistance against the antibiotic. Drug resistant TB requires an even longer treatment of up to 1.5 years with a toxic mix of antibiotics. Therefore, there is an urgent need for novel antibiotics with a shorter treatment time that are less prone to resistance. The RespiriTB projects aims to develop novel antibiotics that target the Mtb respiratory pathway, the energy centre of the bacterium. Treatment will be combined with the recently developed antibiotic bedaquiline that also targets the Mtb respiratory pathway, thus creating a double blow to the bacterium. RespiriTB will also cast a wider net in search for novel antibiotics, by targeting other essential Mtb proteins. In addition, the project will target human factors that are needed for Mtb to survive in the infected host. Our development of novel antibiotics with shorter treatment time and that are less prone to drug resistance will be an essential factor in the fight against TB, the deadliest infectious disease world-wide.