We describe the development and implementation of an instructional design that focused on bringing multiple forms of active learning and student-centered pedagogies to a one-semester, undergraduate introductory biology course for both majors and nonmajors. Our course redesign consisted of three major elements: 1) reordering the presentation of the course content in an attempt to teach specific content within the context of broad conceptual themes, 2) incorporating active and problem-based learning into every lecture, and 3) adopting strategies to create a more student-centered learning environment. Assessment of our instructional design consisted of a student survey and comparison of final exam performance across 3 years-1 year before our course redesign was implemented (2006) and during two successive years of implementation (2007 and 2008). The course restructuring led to significant improvement of self-reported student engagement and satisfaction and increased academic performance. We discuss the successes and ongoing challenges of our course restructuring and consider issues relevant to institutional change.