Although leprosy is caused by an infectious agent (Mycobacterium leprae or M. lepromatosis), most of the heavily exposed population—the household and family members of patients—will not develop leprosy during their lifetime. This group is considered at highest risk for developing leprosy, but only 3% – 5% will progress to the disease. Inherent to the current method of diagnosis of leprosy (i.e., detection of clinical symptoms such as skin patch with loss of sensation, enlarged peripheral nerves), the disease is often diagnosed late. Furthermore, although multidrug therapy (MDT) is effective, the number of new cases has been stationary for the past 15 years—indicating that treatment does not block transmission. In the past 25 years, immunoprophylaxis (with BCG vaccination) and, more recently, chemoprophylaxis (e.g., single-dose rifampin [SDR]) have proved effective in preventing leprosy in household contacts. Indeed, the 2018 WHO guidelines support this chemoprophylaxis approach, which is likely to be a successful, short-term strategy aimed at identifying new cases and treating healthy social and household contacts to impact incidence. Nevertheless, efforts are clearly needed to improve early identification of leprosy patients and to identify and treat infected persons—especially in low-to-middle endemic areas where the use of large-scale chemoprophylaxis would not be cost-effective in controlling transmission and reducing incidence. To reach these goals and contribute to zero leprosy, progress is needed in clinical and laboratory-based diagnosis as well as translation of the latter to rapid, user-friendly field tests.