Guillain-Barré syndrome (GBS) is an inflammatory disorder and an acute immune-mediated demyelinating neuropathy that causes reduced signal transmissions, progressive muscle weakness, and paralysis. The etiology of the syndrome still remains controversial and uncertain. GBS can be initiated and triggered by respiratory tract infections such as influenza, and intestinal infections such as . In addition, there is considerable evidence suggesting links between influenza vaccination and GBS. As reported previously, the incidence of GBS in individuals receiving swine flu vaccine was about one to two cases per million. Despite the influenza vaccine efficacy, its association with an immune-mediated demyelinating process can be challenging as millions of people get vaccinated every year. In this review we will discuss the association between influenza infection and vaccination with GBS by focusing on the possible immunopathological mechanisms.