The associations between exposure to infectious agents and the development of autoimmune diseases have been established in numerous studies and almost every autoimmune disease has been linked to one infection or another. Different infectious agents, namely bacteria, viruses and parasites, were found to be related to autoimmunity via several mechanisms such as molecular mimicry, epitope spreading, polyclonal activation of B-cells and finally by bystander activation of T-cells and antigen presenting cells. The links between infections and autoimmunity are complex, on the one hand many infectious agents were found to be pathogenic, while on the other hand, others might induce protection from autoimmunity. In addition, many patients suffering from autoimmune diseases are especially vulnerable for infections, due to the underlying disease and the frequent use of immunosuppressive therapy. Thus, vaccination to prevent and reduce infectious morbidity and mortality is recommended for this group of patients. Alas, vaccines which contain infectious antigens, either attenuated or recombinant, may induce, although rarely, autoimmunity via similar ‘infectious’ mechanisms. Furthermore vaccines contain other excipients such as adjuvants and preservatives which may induce an immune mediated response. Adjuvants are included in most human vaccines in order to increase the protective immune response to infectious antigens, however in recent years many adjuvants were found to induce autoimmunity by themselves. Similarly to the autoimmune manifestation following silicone implantation, especially following rupture and leak of silicone, previously termed ‘adjuvant disease’, it seems also that adjuvants which are included in human vaccines may rarely induce autoimmunity. Recently, a new disease of autoimmune nature was defined and termed macrophagic myofaciitis. This syndrome appears in subjects who are genetically susceptible following vaccination with alum adjuvanted vaccines, and it is characterized by an active lesion with evidence of alum mediated reaction at the site of inoculation. Genetic susceptibility is a cardinal factor in the mosaic of autoimmunity and may determine the individual response to a certain infectious agents, a drug or a vaccine. Fortunately, it seems that genetic and other factors render a low rate of susceptibility to autoimmunity following vaccination, and therefore vaccines’ beneficial effects outweigh the risks of autoimmunity for the vast majority of individuals. In this special issue of Lupus we have assembled a collection of manuscripts describing the multifaceted associations between infections, vaccines and autoimmune diseases, as well as the mechanisms by which autoimmunity is inflicted and the genetic susceptibility related to these unique interactions.