The neurotrophin brain-derived neurotrophic factor (BDNF) is ubiquitous in the central nervous system (CNS) throughout life. In addition to trophic effects on target neurons, BDNF appears to be part of a general mechanism for activity-dependent modification of synapses in the developing and adult nervous system. Thus, diseases of abnormal trophic support (such as neurodegenerative diseases) and diseases of abnormal excitability (such as epilepsy and central pain sensitization) can be related in some cases to abnormal BDNF signaling. For example, various studies have shown that BDNF is upregulated in areas implicated in epileptogenesis, and interference with BDNF signal transduction inhibits the development of the epileptic state. Further study of the cellular and molecular mechanisms by which BDNF influences cell survival and excitability will likely provide novel concepts and targets for the treatment of diverse CNS diseases.