Introduction A well-designed food frequency questionnaire (FFQ) aims to assess habitual intake of foods or nutrients of interest in the target population. Therefore, the food list of an FFQ has to be adapted to the prevailing dietary habits of the target population and updated when re-used some time after initial development. However, due to lack of expertise, time, or finances, FFQs are often re-used without adaptations. To simplify and standardize the development of new FFQs, we developed a computer system, the Dutch FFQ-TOOLTM, to generate, apply, and process FFQs. The aim of this thesis was to provide the scientific basis for development of this system. Methods We first characterized FFQ design by a systematic review of validation studies. For selecting food items in the system, we evaluated a simple procedure, called MOM2, which selected food items on the basis of explained variance in nutrient intake without taking covariance from other food items into account. To improve questions in FFQs, we conducted focus group discussions to investigate problems encountered by adults when filling out FFQs. Using the information from these studies; we developed a prototype of the system, which used the Dutch National Food Consumption Survey 1998 for the selection of food items. This prototype was used to generate an FFQ, which was subsequently validated against biomarkers and 3-day food records. Results In the systematic review, we observed that FFQs with more items (>200 items) were better able to rank people according to their intake of most nutrients than shorter FFQs (<100 items). MOM2 appeared suitable to select food items that contributed importantly to variance in nutrient intake, leading to only a few more food items than regression analysis. Focus group discussions showed that 36 out of 40 respondents were confused by examples that were meant to clarify questions and 31 out of 40 respondents had difficulties in identifying consumed foods, because categorization of foods was not logical to them. This ...