Over 81% of US immigrants were born in a Latin American, Caribbean, or Asian country. The “immigrant paradox” is the long-standing observation in medical and social science research that immigrants exhibit better health profiles than US natives, despite their disproportionate concentration in low socioeconomic status positions. While the empirical evidence suggests that immigrant health advantages deteriorate with greater duration of US residence and across subsequent generations, the role of acculturation within the immigrant paradox is unclear. Herein, we summarize the contemporary health literature on Latino and Asian US immigrant adults (the two largest US immigrant subpopulations), review explanations for the immigrant paradox (psychosocial and behavioral, sociological, and methodological explanations), and discuss important trends and implications for health promotion and disease prevention. Systematic research to identify determinants of US immigrant health, including their sociodemographic and life-course modifiers, may help uncover promising intervention targets for health promotion and positive adaptation.