To address the need for effective, efficient ways to apply active learning in undergraduate biology courses, in this paper, we propose a problem-centered approach that utilizes supplemental web-based instructional materials based on principles of active learning. We compared two supplementary web-based modules using active learning strategies: the first used Merrill's First Principles of Instruction as a framework for organizing multiple active learning strategies; the second used a traditional web-based approach. Results indicated that (a) the First Principles group gained significantly from pretest to posttest at the Remember level (t(40) = -1.432, p = 0.08, ES = 0.4) and at the Problem Solving level (U = 142.5, N1 = 21, N2 = 21, p = 0.02, ES = 0.7) and (b) the Traditional group gained significantly from pretest to posttest at the Remember level (t(36) = 1.762, p = 0.043, ES = 0.6). Those in the First Principles group were significantly more likely than the traditional group to be confident in their ability to solve problems in the future (?[superscript 2] (2, N = 40) = 3.585, p = 0.09).