The Sri Lankan Twin Registry (SLTR), established in 1997, is a unique resource for twin and genetic research in a low- and middle-income country (LMIC). It comprises of a volunteer cohort of 14,120 twins (7,060 pairs) and 119 sets of triplets, and a population-based cohort of 19,040 (9,520 pairs) twins and 89 sets of triplets. Several studies have been conducted using this registry, including the Colombo Twin and Singleton Study (CoTaSS 1; 4,387 twins, 2,311 singletons), which have explored the prevalence and heritability of a range of psychiatric disorders as well as gene-environmental interplay. Currently, a follow-up study (CoTaSS 2) of the same cohort is underway, looking at the prevalence and interrelationship of key cardiovascular and metabolic risk markers (e.g., metabolic syndrome). A significant feature of CoTaSS 2 is the establishment of a biobank. Current SLTR work is extending beyond mental health and the interface between mental and physical health to new horizons, extending collaborations with the wider global twin research community. Ethics and governance have been given special emphasis in the initiative. Capacity building and public engagement are two crucial components. Establishment of a state-of-the-art genetic laboratory was a major accomplishment. SLTR is a classic showcase of successful North–South partnership in building a progressive research infrastructure in a LMIC.