In an increasing number of central nervous system (CNS) diseases a pathogenic contribution of the immune system is proposed. However, the exact underlying mechanisms are often poorly understood. The collection of articles in this special issue presents a state-of-the-art review of adaptive and innate immune mechanisms and their main players in number CNS disorders. The aim of these articles is to stimulate discussion on the question whether the immune system may be a feasible target of therapy for diseases where currently no effective treatment exists.