This dissertation is about inquiry-based teaching with computer simulations in science education. Research of the past decade shows that instruction can be enhanced by using computer simulations. For example, it can be an effective tool to prepare for laboratory activities. How to use computer simulations for teaching practices, however, is relatively unknown. How to teach with simulations is the main topic of the studies in this dissertation. Computer simulations allow for student-centered, inquiry-based teaching and learning. Our studies show that simulations are not only experienced as appropriate for learning individually or in small groups, but also at the whole-class level. Investigating teaching with computer simulations at the whole-class level is complex, due to the wide range of impacting variables. Our method to investigate the student-centered, inquiry-based character of teacher-student interaction reveals that zooming in on contextual mechanisms is essential for understanding teaching with computer simulations.