This study explored the relation between pedagogical knowledge and subject-matter knowledge, in the context of inquiry-driven science instruction, and their relation to instructors' performance in the instructional process. This multiple case study focused on three distinct categories of teachers-Novice in Inquiry and in Science, Novice in Inquiry and Expert in Science, and Expert in Inquiry and in Science-and examined the commonalities and differences among them by exploring the cognitive processes these teachers used when planning and enacting an inquiry instructional situation, as well as when assessing students' learning resulting from this specific instructional event.