This article provides a comprehensive review of the recent literature on Native Hawaiian youth and substance use. Eight-hundred and twelve potential articles pertaining to Native Hawaiian youth and substance use published between 1995 to May 2009 were identified through an exhaustive literature search. The total number of articles was reduced to 32 articles, which were systematically coded and content analyzed. The findings indicated that the majority of studies focused on epidemiology, with relatively few of them focused on causal factors/etiology and systematic program development or evaluation. Gender differences in drug use were highlighted in several studies. Implications for culturally tailored interventions and future research are discussed.