Despite substantial improvements in global tuberculosis (TB) control over the past 2 decades, TB remains the ninth leading cause of death worldwide and the leading cause of death from a single infectious agent. From the perspective of both TB control programs and treating clinicians, rapid diagnosis of active pulmonary TB is crucial to identify potentially infectious persons, facilitate prompt initiation of treatment, and mitigate transmission. Although sputum smear microscopy and mycobacterial culture have traditionally been used for diagnosis, molecular diagnostic methods have evolved considerably over the past 2 decades, both in public health and clinical laboratory settings. Among these methods, Xpert MTB/RIF has revolutionized TB diagnosis in low-income and middle-income countries, enabling rapid initiation of treatment and infection control interventions. In parallel with continued optimization of their performance, increased access, implementation, and effectiveness evaluations of emerging diagnostic tools will be an important component of ongoing TB elimination strategies.