Leprosy, a neglected tropical disease, causes significant morbidity in marginalized communities. Before the COVID-19 pandemic, annual new case detection plateaued for over a decade at ~200,000 new cases. The clinical phenotypes of leprosy strongly parallel host immunity to its causative agents Mycobacterium leprae and Mycobacterium lepromatosis. The resulting spectrum spans from paucibacillary leprosy, characterized by vigorous pro-inflammatory immunity with few bacteria, to multibacillary leprosy, harbouring large numbers of bacteria with high levels of seemingly non-protective, anti-M. leprae antibodies. Leprosy diagnosis remains clinical, leaving asymptomatic individuals with infection undetected. Antimicrobial treatment is effective with recommended multidrug therapy for 6 months for paucibacillary leprosy and 12 months for multibacillary leprosy. The incubation period ranges from 2 to 6 years, although longer periods have been described. Given this lengthy incubation period and dwindling clinical expertise, there is an urgent need to create innovative, low-complexity diagnostic tools for detection of M. leprae infection. Such advancements are vital for enabling swift therapeutic and preventive interventions, ultimately transforming patient outcomes. National health-care programmes should prioritize early case detection and consider post-exposure prophylaxis for individuals in close contact with affected persons. These measures will help interrupt transmission, prevent disease progression, and mitigate the risk of nerve damage and disabilities to achieve the WHO goal ‘Towards Zero Leprosy’ and reduce the burden of leprosy.