(1) Background: The global burden of leprosy is not shared equally; with the majority of cases being diagnosed in Brazil, India, and Indonesia. Understanding the methods of active case detection (ACD) used in high and low endemic regions is vital for the development of future screening programs. (2) Methods: A systematic search of three databases, PubMed, Embase and Web of Science, was conducted for English language papers, published since the year 2000, which discussed the use of active case detection methods for leprosy screening. The paper utilised the Integrated Screening Action Model (I-SAM) as a tool for the analysis of these methods. (3) Results: 23 papers were identified from 11 different countries. The papers identified 6 different methods of active case detection: Household contact/social contact identification; door-to-door case detection; screening questionnaire distribution; rapid village surveys; school-based screening; and prison-based screening. 15 were located in high endemic regions and 8 of these were located in low endemic regions. (4) Conclusions: For selecting the appropriate methods of active case finding, the leprosy endemicity must be taken into consideration. The findings contribute to policy decision making allowing for more successful future leprosy case detection programs to be designed, ultimately reducing the global burden of the disease, and achieving the WHO’s aim of zero leprosy.