SG100K is a comprehensive, long term study focussed on the health and well-being of the Singapore population. The study has been set up with core funding from NMRC, as a partnership between leading researchers at the Lee Kong Chian School of Medicine at NTU, the National University of Singapore, the Singapore Eye Research Institute, the National Heart Centre, Singapore, and their associated healthcare partners. SG100K aims to engage the participation of more than 100,000 people who are broadly representative of our diverse, multi-ethnic community. We collect detailed baseline health information (e.g., waist-hip measurement, blood pressure, fitness, eye acuity, cholesterol level, blood sugar, cognitive assessment, health and lifestyle assessment through a structured questionnaire, etc.) and biological specimens from participants. We recruit men and women of Chinese, Malay and Indian ethnicity into the study. This inclusive strategy will enable population-based research in groups that have been historically under-represented. We will monitor long-term health outcomes of SG100K participants through a combination of approaches, including electronic medical records, disease registers and invitations for further follow-up. We will use the information and samples collected to identify the social, environmental, lifestyle and genetic factors that are associated with diabetes, hypertension, cancer and other important diseases in the multi-ethnic population of Singapore. Our sample size of 100,000 people will put us in a strong position to address key questions about health and disease with precision. The SG100K study will be an internationally outstanding resource for understanding and promoting the health of Singaporeans, and will yield results of regional and global significance.