Data from randomized controlled trials (RCTs) provide the strongest evidence for establishing relations between exposures, including dietary exposures, and health outcomes. However, not all diet and health outcome relations can be practically or ethically evaluated by using RCTs; therefore, many dietary recommendations are supported by evidence primarily from observational data, particularly those from prospective cohort studies. Although such evidence is of critical importance, limitations are often underappreciated by nutrition scientists and policymakers. This editorial review is intended to 1) highlight some of these limitations of observational evidence for diet-disease relations, including imprecise exposure quantification, collinearity among dietary exposures, displacement/substitution effects, healthy/unhealthy consumer bias, residual confounding, and effect modification; and 2) advocate for greater caution in the communication of dietary recommendations for which RCT evidence of clinical event reduction after dietary intervention is not available.