The ASM Curriculum Guidelines recommend that undergraduate microbiology courses should cover a wide variety of content ideally utilizing active learning approaches, which promote participation and enhance student success. However, in content-heavy courses, it can be easier to revert to traditional lecture-based teaching. Here, we describe a case series designed to increase student engagement and connect course concepts by exploring a single microbe in the context of different learning objectives. In this case series, respiratory syncytial virus (RSV) is used due to its fascinating history, well-described biology, and current clinical relevance, as well as recently described advances in creating a vaccine for RSV. This four-part case series can be embedded across several units of a general microbiology course as individual “explorations,” and employs multiple, evidence-based pedagogical approaches including case-based learning, engaging with primary literature, jigsaw strategy, analysis of real-world data sets, and whole-class discussion. Each exploration is designed to cover or expand on key concepts in microbiology, including milestones in the history of the field, Koch’s postulates and the germ theory of disease, the discovery of viruses, virus structure and replication, clinical epidemiology, and vaccines. Throughout the course, students work individually, in pairs, and in small groups to complete the activities, which take place predominantly during class. Student feedback indicates that they enjoy these activities as an alternative to traditional lecturing. This case series enables students to build connections between course concepts, assemble higher-order thinking about diverse topics in Microbiology, and apply their learning to real-world examples and scenarios.