Vaccine-related adverse events are uncommon and typically mild. Children may experience conditions such as rashes, fevers, syncope, protracted crying, or seizures shortly after receiving their routine immunizations. When children are brought to the emergency department or clinic to be evaluated for one of these conditions, the health care provider may be called upon to determine the likelihood that it was caused by a recently administered set of vaccines. This determination has substantial implications for medical care, including the safety of administering future vaccines. This article reviews the current understanding of vaccine-related adverse events. Using this information, clinicians should be able to identify those events likely to be related to vaccine administration and those that are not. The appropriate management of vaccine-related adverse events is also discussed.