As part of ongoing efforts to enhance teaching practices in a large-class introductory biochemistry course, we have recently tested the effects of using a student response system (clickers) on student exam performances and engagement with the course material. We found no measurable difference in class mean composite examination score for students taught with clickers than for those taught in traditional lectures. However, there were significantly more students in the highest achievement category (91–100%) in the section that incorporated clickers than in any other section over five academic terms. Overall, students gave high approval ratings for the use of the clickers, particularly in increasing their participation and engagement in lectures. However, students who reported their performance to be in the lowest performance categories gave a lower level of approval for the use of the clickers than those who reported their performance to be in the higher performance categories. The implications for using clickers to improve teaching in biochemistry are discussed.