The NIH BRAIN initiative, informed by the report from the scientific community (BRAIN 2025) is underway. The major funded efforts at this time fit into 3 main categories; 1) defining the components of brain circuits, i.e., a cell census; 2) developing and testing tools for recording high density information on circuit structure, activity, and manipulating circuit activity; 3) novel technology for noninvasive interrogation and manipulation of circuit activity (next generation imaging). The BRAIN oversight committee provides guidance to NIH as we move forward to engage scientists from computation and physical sciences as well as neuroethics in this historic undertaking. BRAIN is poised to develop the neurotechnologies that enable exploration of the neural basis of human behavior as well as the circuit dysfunction that underlies the disability of neuro/mental/substance abuse disorders.