Abstract Background In the United States (U.S.), the prevalence of both diagnosed and undiagnosed type 2 diabetes (T2D) is nearly twice as high among Mexican-origin Hispanic/Latino adults compared to non-Hispanic Whites. Rates of diabetes-related complications, e.g., acute stroke and end-stage renal disease, are also higher among Hispanic/Latino adults compared to their non-Hispanic/Latino White counterparts. Beyond genetic and biological factors, it is now recognized that sociocultural influences are also important factors in determining risk for T2D and the associated complications. These influences include ethnicity, acculturation, residence, education, and economic status. The primary objective of this study is to determine the influence of the 5 major determinants of human health (genetics, biology, behavior, psychology, society/environment) on the burden of T2D for Latino families. To achieve this objective, Mil Familias (www.milfamilias.sansum.org/) is establishing an observational cohort of 1000 Latino families, with at least one family member living with T2D. Methods Specially trained, bilingual Latino/a community health workers (Especialistas) recruit participant families and conduct research activities. Each individual family member will contribute data annually on over 100 different variables relating to their genetics, biology, psychology, behavior, and society/environment, creating a Latino-focused biobank (“Living Information Bank”). This observational cohort study is cross-sectional and longitudinal. Participants are divided into 4 groups: adults age ≥ 18 years with and without T2D, and children age ≥ 7 and