In the U.S., foodborne disease causes millions of illnesses annually, resulting in thousands of deaths. To reduce food poisoning, restaurant food handlers need accurate knowledge of food safety principles as a starting point for the outcome of optimal food safety behavior. The study described in this article determined food safety knowledge gaps among suburban Chicago restaurant food handlers. A cross-sectional survey of 729 food handlers at 211 suburban Chicago restaurants was conducted from June 2009 through February 2010. A 50-question survey was administered by a trained interviewer in either English or Spanish. Mixed-effects regression analysis identified risk factors associated with an overall food safety knowledge score. The mean overall knowledge score was only 72% and substantial knowledge gaps related to cross contamination, cooking, and holding and storage of food were identified. Spanish-speaking food handlers scored significantly lower than English-speaking food handlers (p < .05). Although certified food managers scored significantly higher than noncertified food handlers, their score was only 79%. These data provide targets for educational interventions to remedy knowledge gaps in food handlers in order to prevent food poisoning from restaurants.