This article discusses a number of issues that must be considered when investigating the behavioral effect of foods. These issues include the idiosyncratic response to a specific food, the necessity of identifying the individual sensitive to the food being studied, the necessity of including a washout phase, consideration of withdrawal effects, assessment of change, dietary challenges, and the time parameter necessary for the effect to be demonstrated. These issues must be considered during the design phase to maximize the probability of detecting the true behavioral effect of a specific food or combination of foods.