A systematic review of the literature on dietary patterns (multiple dietary components operationalized as a single exposure) in relation to nutrient adequacy, lifestyle and demographic variables, and health outcome was conducted. Most of the published reports on the subject have used one of two methods to determine dietary patterns: (a) diet indexes or scores that assess compliance with prevailing dietary guidance as dietary patterns, and (b) data-driven methods that use factor or cluster analysis to derive dietary patterns. Irrespective of the approach used, patterns characterized by fruit/vegetable/whole grain/fish/poultry consumption generally have been reported to relate to micronutrient intake, and to selected biomarkers of dietary exposure and disease risk in the expected direction. Age, income, and education have been reported to be among positive predictors of the so-called more healthful dietary patterns. An inverse association of healthful dietary patterns with all-cause mortality and cardiovascular disease risk was reported in most studies. However, the magnitude of risk reduction was modest and was attenuated after control for confounders. Few published studies showed an association between risk of most incident cancers and dietary patterns. Both of the currently used approaches for extracting dietary patterns have limitations, are subject to dietary measurement errors, and have not generated new diet and disease hypotheses.