Our main goal in this study was to explore whether the use of models in high school molecular genetics instruction can contribute to students' understanding of concepts and processes in genetics. Three hundred and nineteen students from four comparable groups of 11th- and 12th-grade students participated. The control group (116 students) was taught using the traditional lecture format, while the others received instruction that integrated one of the following models: Bead model (71 students), computer simulation (61 students), or illustrations typically used in textbooks (71 students). Each group was provided with similar instructions and the same guiding questions. We used two assessment instruments; a written questionnaire and personal interviews. The written questionnaire (post-test) comprised 10 open-ended and 13 multiple-choice questions. Six of the multiple-choice questions were also given to students before receiving their genetics instruction (pre-test). We conclude that it is worthwhile to integrate activities with specific instructions and guiding questions in the teaching of molecular genetics in high school. Moreover, the open-ended questions brought out the differences among the groups, revealing that activities with the bead model and computer simulation were significantly more effective than the illustration activity. (This paper is a summary of Marbach-Ad, Rotbain, & Stavy, 2005; Marbach-Ad, Rotbain, & Stavy, 2008; Rotbain, Marbach-Ad, & Stavy, 2005; Rotbain, Marbach-Ad, & Stavy, 2006; Rotbain, Marbach-Ad, & Stavy, 2008.)