Tuberculosis (TB) has emerged as the leading infectious cause of death globally. New paradigms are needed to reduce TB rates and mortality. Programs harnessing the potential of community health workers (CHWs) to enhance TB prevention and care have shown great promise. In this perspective article, we review the history of CHW-based efforts to prevent and treat TB, present evidence illustrating the effectiveness of CHWs across the entire cascade of TB care, and outline additional opportunities for CHWs to address challenges particular to the TB pandemic. Despite many promising studies, knowledge gaps persist and we suggest an agenda for future research on the role of CHWs in TB prevention and care.