Autoimmune diseases are systemic or organ-specific disorders that are the result of an attack of the immune system against the body's own tissue. Development of autoimmune disease is generally avoided by distinct mechanisms that silence adaptive self-reactive T or B cells. The innate immune system is critically involved in the defense against pathogens and the induction of primary adaptive immune responses. Toll-like receptors (TLRs) are key receptors that activate the innate immunity in response to pathogen recognition. Recent data show that activation of innate immune cells such as dendritic cells (DCs) can break this state of tolerance and induce autoimmunity by priming autoreactive T cells. Here we review recent examples of how innate immune responses influence the adaptive immunity in the induction or regulation of autoimmune disease.