We are in the midst of a revolution in the genomic sciences that will forever change the way we view biology and medicine, particularly with respect to brain form, function, development, evolution, plasticity, neurological disease pathogenesis and neural regenerative potential. The application of epigenetic principles has already begun to identify and characterize previously unrecognized molecular signatures of disease latency, onset and progression, mechanisms underlying disease pathogenesis, and responses to new and evolving therapeutic modalities. Moreover, epigenomic medicine promises to usher in a new era of neurological therapeutics designed to promote disease prevention and recovery of seemingly lost neurological function via reprogramming of stem cells, redirecting cell fate decisions and dynamically modulating neural network plasticity and connectivity. Ann Neurol 2008;64:602–617