Mycobacterium tuberculosis (Mtb) causes tuberculosis (TB), one of the world’s most deadly infections. Mtb has infected humans for millennia and is highly adapted to navigate the complexity of the human immune system. In most infected individuals, a delicate balance is established that allows Mtb to persist without causing disease. In approximately 10% of infected people, the balance tips in favor of the bacteria, resulting in active TB. What accounts for successful host resistance to Mtb and why does it fail in 10% of infected individuals? We are identifying and characterizing host-pathogen interactions that underlie the detente between Mtb and its human host. Our work is providing mechanistic insight into how Mtb alters cellular trafficking, antigen presentation, and metabolism of macrophages and dendritic cells. In studying the molecular mechanisms by which Mtb sabotages cellular functions, we hope to better understand host immunity and bacterial pathogenesis. This basic understanding will ultimately allow us to tip the balance in favor of the host.