The mechanisms of the antibody-dependent enhancement (ADE) of viral infection are presented, particularly within the Picornaviridae family. The ADE of infection has been described in both human and animal models, worsens viral infections and compromises vaccine safety. The ADE of coxsackievirus B infection can also be implied in the pathogenesis of diseases like chronic dilated cardiomyopathy or insulin-dependent type 1 diabetes.