With enrollment in the fields of science, technology, engineering, and mathematics (STEM) shrinking, teachers are faced with the problem of appealing to a new generation of students without sacrificing educational quality. Evidence has shown that this problem can be reduced with the use of a number of pedagogical strategies of which project-based learning (PBL) is one. PBL addresses the fundamental challenge of increasing students’ motivation, their mastery of course material, and finding applications for what they have learned to apply in various situations. This study demonstrates the benefits of redesigning a standard lab-based molecular biology course to create a more effective learning environment. Using PBL, students who enrolled in Bio-251 at Harold Washington College in Chicago were given the responsibility of cloning a bacterial gene from one species into a new host species. They were then tasked with the expression and purification of the resulting protein for future research purposes at University of Illinois-Chicago, a leading 4-year research institute. With use of the PBL method, students showed improvement in the areas of self-confidence, lab technical skills, and interest in STEM-related fields and, most of all, the students showed a high level of performance and satisfaction.