After a new reassortant swine influenza A H1N1 virus caused outbreaks in Mexico and the United States in 2009, a vaccine was prepared from this virus to immunize the entire US population. Surveillance for Guillain-Barré syndrome (GBS) after receipt of this vaccine was carried out in 3 populations: the Vaccine Safety Datalink Project, the 10 Centers for Disease Control and Prevention Emerging Infections Program sites, and a network of large insurance companies. These studies found a small increase of approximately 1 case of GBS per million vaccinees above the baseline rate, which is similar to that observed after administration of seasonal influenza vaccines over the past several years. Enhanced surveillance for GBS was conducted in 2009-2010 because of the experience in 1976 of 362 GBS cases' occurring during the 6 weeks after influenza vaccination of 45 million persons, an 8.8-fold increase over background rates. The 1976 mass immunization had been conducted to prevent an influenza epidemic from another swine influenza A H1N1 recombinant virus. It can be concluded from these recent studies that influenza vaccination overall is of public health benefit, helping to reduce mortality and prevent the thousands of deaths that occur from annual seasonal influenza outbreaks, despite the possibility of a small increased risk of GBS associated with influenza vaccines.