Guillain-Barré syndrome (GBS) is an acute, immune-mediated polyradiculoneuropathy that can result in progressive muscle weakness, paralysis, and, in severe cases, respiratory failure. While the majority of GBS cases are preceded by infectious events, concerns about a potential link between vaccines and GBS have periodically arisen. This commentary examines existing information on the association between GBS and vaccines and reviews the epidemiology, pathogenesis, and infectious and noninfectious triggers of GBS. GBS incidence rates are influenced by age, seasonality, geography, and comorbidities and are increasing over time. The complexities in assessing causality between vaccination and GBS are addressed, including the importance of diagnostic certainty and standardized case definitions. The self-controlled case series study design is most commonly used to investigate potential relationships between vaccines and GBS due to its efficiency (i.e. only vaccinated persons with GBS are included) and ability to control for fixed confounders (e.g. comorbidities), but results may be biased by time-varying confounders (e.g. viral infection activity) and lack of diagnostic confirmation. Further, attributable/excess risk estimates based on such studies are influenced by background/baseline GBS risk, which may differ by studied population. This review aims to inform ongoing research and guide public health risk assessment for this rare adverse event.