In this review we discuss the relationship between commonly administered childhood vaccines such as diphtheria-tetanus-whole cell pertussis (DTP) and measles-mumps-rubella (MMR), and the risk of nonfebrile and febrile seizure. We summarize data from the Vaccine Safety Datalink Study and other studies that suggest that DTP and MMR vaccine are associated with a transiently increased risk of febrile seizures, and cause between 5-9 and 25-34 additional extra febrile seizures per 100 000 immunized children, respectively. DTP and MMR do not appear to increase the risk of nonfebrile seizures. We discuss some methodologic challenges in studies of vaccines and seizures. Because there is no adequate comparison group that would allow for the study of seizures long after vaccination, studies of seizures are limited to acute events shortly following vaccination. Additionally, while seizures following vaccination are worrisome to parents and physicians alike, observational studies of the neurodevelopmental outcomes of these children are particularly problematic. We discuss how such studies are confounded by the natural history of predisposition to febrile seizures and by the increased diagnostic scrutiny that children with febrile seizures might undergo. Nevertheless, current data suggest that children with febrile seizures do not experience long-term negative effects.Finally, we discuss the creation of new clinics designed specifically to assist physicians in managing the vaccination of children with a personal or family history of seizures. Data from these clinics suggest that vaccination is safe for children with a personal or family history of seizures, but statistical power has been limited. We conclude by discussing the introduction of new vaccines, and note that, even with widespread use, it will take many years before we can be knowledgeable about the risk of rare events with these newly licensed products.