The regression discontinuity design (RDD), first proposed in the educational psychology literature and popularized in econometrics in the 1960s, has only recently been applied to epidemiologic research. A critical aim of infectious disease epidemiologists and global health researchers is to evaluate disease prevention and control strategies, including the impact of vaccines and vaccination programs. RDDs have very rarely been used in this context. This quasi-experimental approach using observational data is designed to quantify the effect of an intervention when eligibility for the intervention is based on a defined cutoff such as age or grade in school, making it ideally suited to estimating vaccine effects given that many vaccination programs and mass-vaccination campaigns define eligibility in this way. Here, we describe key features of RDDs in general, then specific scenarios, with examples, to illustrate that RDDs are an important tool for advancing our understanding of vaccine effects. We argue that epidemiologic researchers should consider RDDs when evaluating interventions designed to prevent and control diseases. This approach can address a wide range of research questions, especially those for which randomized clinical trials would present major challenges or be infeasible. Finally, we propose specific ways in which RDDs could advance future vaccine research.