The essence of the immune system is built on two separate foundation pillars: one is specific or adaptive immunity which is characterized by relatively slow response kinetics and the ability to remember. The other is nonspecific or innate immunity exhibiting rapid response kinetics but lacking memory. Lymphocytes are the key players of the adaptive immune system. Each lymphocyte expresses antigen receptors of unique specificity. Upon recognizing an antigen via the receptor, lymphocytes proliferate and develop effector function. Few lymphocytes exhibit specificity for a given antigen or pathogen and massive proliferation is usually required before an effector response can be measured. Hence, the slow kinetics of the adaptive immune system. Because a significant proportion of the expanded lymphocytes survive and may maintain some effector function after elimination of the antigen, the adaptive immune system reacts faster when encountering the antigen a second time. This is the basis of its ability to remember. In contrast to the situation with lymphocytes, where specificity for a pathogen is confined to few cells that must expand to gain function, the cells and molecules of the innate immune system are usually present in massive numbers and recognize a limited number of invariant features associated with pathogens (1). Examples of such patterns include LPS, nonmethylated CG-rich DNA (CpG), or double-stranded RNA, which are specific for bacterial and viral infections, respectively. Most research in immunology has focused on the adaptive immune system and only recently has the innate immune system entered the focus of interest. Historically, the adaptive and innate immune system were treated and analyzed as two separate entities that had little in common. Such was the disparity that few researchers wondered why antigens were much more immunogenic for the specific immune system when applied with adjuvants that stimulated innate immunity (2–4). However, the answer posed by this question is critical to our understanding of the immune system and for comprehending the balance between protective immunity and autoimmunity. This commentary tries to highlight a few important links between the innate and adaptive immune systems and how those may impinge on the course of autoimmune diseases.