Endomyocardial fibrosis (EMF) is a poverty-related disease of unknown origin that afflicts predominantly young people of certain rural areas in low-income countries and can be used to expose global disparities in cardiovascular research. Despite affecting predominantly young people and causing high morbidity and mortality, efforts to understand its mechanisms and natural history have been hampered by the incapacity to detect the early stages of the disease in endemic areas. Dietary, environmental and infectious factors seem to combine in susceptible individuals to give rise to an inflammatory process that leads to endomyocardial damage and scar formation. Lack of awareness by health professionals and low access to health care determine late diagnosis, when complications such as chronic heart failure, thromboembolism and arrhythmia are already present. Open-heart surgery to detach the endocardial fibrous tissue and repair the atrioventricular valve, remains the last resource to prolong patients' survival. Community-based research is therefore needed to understand the epidemiology of EMF, detect early disease, uncover its pathogenesis and explore new therapeutic targets. Our research has shown that echocardiographic screening using standard criteria adds sensitivity and precision to the diagnosis, particularly in asymptomatic disease, providing an opportunity for longitudinal community-based research. However, researchers face major constraints in rural settings where EMF is endemic, including socioeconomic, cultural, geographical and administrative barriers. In presenting our experience we aim to describe the challenges and discuss the lessons learned while implementing community-based research in a highly endemic area in southern Mozambique, one of the poorest countries in the world. Additionally, we discuss how recent advances in medicine-such as use of point-of-care diagnostics, heart failure biomarkers and new imaging techniques-may open new possibilities for high quality research through collaborative partnerships and regional initiatives. 2020 Cardiovascular Diagnosis and Therapy. All rights reserved.