Effective use of active learning techniques remains a challenge in STEM disciplines. We will present our success with Genetics 564, a 100% active learning-based undergraduate capstone course on Genomics and Bioinformatics. Genetics 564 is devoid of ‘traditional’ lecture-based teaching. Students learn about bioinformatic techniques through the reading and presentation of primary literature, and apply this knowledge to their research project as they analyze a human disease gene. The culmination of students' research is the writing of a set of specific aims and the publication of a website detailing their results. Students also engage in an iterative process of peer review throughout the semester. This course uses active learning to provide students with presentation, research, and peer review experiences similar to those used by scientists. In Genetics 564, we have observed that, with direction, undergraduate students can utilize both primary literature and bioinformatic databases to design experiments and test hypotheses. Additionally, students constantly peer- and self-review their presentations and scientific writing, a second layer of active learning that challenges them to not only produce high-quality research but also to critique their work, an important aspect of a truly active classroom. Tasks such as these are usually reserved for graduate level students and higher. The success of the students in our course has demonstrated its utility for teaching students scientific presentation, writing, research, and review skills, and student responses to the course have been overwhelmingly positive. Altogether, this suggests that the active and project-based learning we have employed contributes to both students’ success and motivation within our course setting. Given this, we propose that multiple courses across disciplines would benefit from incorporating aspects of the Genetics 564 structure into their undergraduate classroom. All course materials are freely available on the Genetics 564 website (http://genetics564.weebly.com), where one can also find an archive of past student final projects.