In 2014, the National Institutes of Health (NIH) began funding an ambitious research program, the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, with the singular focus of advancing our understanding of brain circuits though development and application of breakthrough neurotechnologies. As we approach the halfway mark of this 10-year effort aimed at revolutionizing our understanding of information processing in the human brain, it is timely to review the progress and the future trajectory of BRAIN Initiative research.