Evidence has emerged over recent years suggesting that trophic factors such as neurotrophic cytokines and neurotrophins may play an important role in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). In mice that lack the neurotrophic cytokine ciliary neurotrophic factor (CNTF), EAE is more severe, suggesting that this molecule may normally contribute to protection of the nervous system from an inflammatory attack. The axonoprotective neurotrophin brain derived neurotrophic factor (BDNF) is not only expressed in immune cells in vitro, but also in MS lesions. Thus, infiltrating immune cells in the central nervous system (CNS) may not only be detrimental, but may also exert a protective effect, a concept referred to as “neuroprotective autoimmunity” Yet, the functional relevance of BDNF during CNS inflammation has not been definitely elucidated so far. BDNF knockout mice die prematurely and thus cannot be investigated in models of autoimmune demyelination. The analysis of recently developed conditional knockout mice with a selective suppression of BDNF production in different subsets of immune cells may improve our understanding of the role of this neurotrophin during autoimmunity of the CNS.