Although the development of next-generation (NextGen) sequencing technologies has revolutionized genomic research and medicine, the incorporation of these topics into the classroom is challenging, given an implied high degree of technical complexity. We developed an easy-to-implement, interactive classroom activity investigating the similarities and differences between current sequencing methodology and three NextGen technologies. The activity uses existing materials created by each of the biotechnology companies that outline their instrumentation and chemistries. Following this activity, students will understand the molecular biology behind these NextGen applications and the similarities to existing Sanger sequencing methods.