Background: Latinos have become the largest minority group in the United States and will represent 25% of the US population by 2050. Latinos experience a disproportionate burden of poverty and poor health outcomes. Objectives: We critically examined the evidence for a link between acculturation and health disparities in Latinos with a focus on type 2 diabetes (T2D) and nutrition-related risk factors and illustrated how acculturation principles can help design a culturally appropriate T2D self-management intervention in Latinos. Design: Evidence presented in this article was drawn from 1) systematic reviews identified through PubMed searches, 2) backward searches that were based on articles cited, 3) experts in the field, and 4) the author's personal files. Results: The preponderance of the evidence supported an association of acculturation with poor dietary quality and obesity. These associations appeared to be modified by several socioeconomic and demographic factors and were not always linear. The association between acculturation and T2D is unclear. Conclusions: Longitudinal studies and more sophisticated analytic approaches are needed to better understand if and how acculturation affects health-disparity outcomes in Latinos. Tailoring interventions to the acculturation level of individuals is likely to help reduce health disparities in Latinos.Am J Clin Nutr 2011;93(suppl):1163S-7S.