We describe here a novel and effective structure to support the replacement of traditional recitation sections in a large upper level biochemistry course with small student-led problem-based learning (PBL) groups (“workshops”) that employ a cooperative learning approach. This is part of an ongoing campus-wide effort to establish and maintain such workshops as a viable and integral component of many undergraduate courses at the University of Rochester. In biochemistry, for each workshop group of 8–10 students, we rely on a student leader, usually recruited from the previous year's pool of top students, whose function is both to guide and to inspire the group effort. A crucial component of our approach is that these leaders participate in a semester-long credit-bearing training course co-taught by the course instructors and an educational specialist. In this course, leaders review the preceding and upcoming weeks' workshops and study selected aspects of learning theory, group dynamics, and diversity training. Overall our workshop leaders feel that they benefit substantially from this training by improving their pedagogical skills in the context of biochemistry, by putting theories about group leadership and learning into practice, and by solidifying their working biochemical knowledge. We believe that the important features of implementing our model (the incorporation of a problem-based learning approach into a student-led small group format) are: 1) the teamwork as co-equals between the course instructors and the educational specialists, 2) the concurrent iterative training of the workshop leaders in a credit-bearing course of study, 3) the built-in leader turnover (normally a frustrating occurrence) as a beneficial component of the course, and 4) the enthusiasm and commitment to biochemistry displayed to current students by their peer leaders.