In the USA type 2 diabetes mellitus affects roughly 9 % of the population with a disproportionate burden in racial/ethnic minorities. The prevalence of diabetes is highest in American Indians/Native Alaskans followed by non-Hispanic blacks, Hispanic Americans, Asian Americans, and non-Hispanic whites. Many causes exist for the disparity in rates of prevalent diabetes spanning from biology and genetics to healthcare delivery and prevention programs for diabetes. Racial/ethnic minorities also have higher rates of microvascular complications suggesting a need for examination of delivery of care, non-pharmacological treatment, and selection of antidiabetes medications. In this article we review the epidemiology, classification, and unique pathophysiological aspects of type 2 diabetes in minority populations in the USA including race/ethnic differences in biological factors (obesity, fat distribution, glucose metabolism, and insulin resistance) and nonbiological factors (acculturation and health behaviors). We evaluate the genomic and epigenetic landscape including novel diabetes-associated single nucleotide polymorphisms (SNPs) and epigenetic factors specific to native populations and underserved communities. We assess the limitations of current diagnostic criteria including racial/ethnic differences in hemoglobin A1c. We examine issues related to management of diabetes in native and underserved populations from a multilevel perspective, beginning with the coordination and delivery of diabetes care services progressing to pharmacologic and non-pharmacological management of diabetes, including lifestyle and surgical interventions. Last, we evaluate the current models of translation of primary prevention of diabetes in native and underserved populations and finish with a discussion of unmet research needs. In this manner we aim to provide a comprehensive review of important aspects of diabetes and its management in native populations and underserved communities.