Eating outside of the home environment on a frequent basis has been associated with weight gain. Food choices when eating out are usually high in energy content, which contributes to excessive energy intake; however, the available data on out-of-home eating and obesity are far from conclusive. This systematic review assesses the association between out-of-home eating and body weight in adults over 18 years of age. The literature databases searched included Medline, Embase, Lilacs, The Cochrane Library, and the ISI Web of Knowledge. The review includes a comprehensive quality assessment of all included observational studies, 20 cross-sectional studies, and 8 prospective cohort studies. All but one of the prospective cohort studies and about half of the cross-sectional analyses found a positive association between out-of-home eating and body weight. However, many methodological differences among the studies were found, such as the definition of out-of-home eating and its assessment, which limits comparisons. The results of the present analysis suggest that in future studies fast-food restaurants and other out-of-home dining venues should be analyzed separately, assessments based on a single 24-h recall should be avoided, and controls for at-home choices (which were not included in any of the studies reviewed) are necessary to evaluate this association.