The purpose of this paper is to review the current state of neuroscience research with a focus on what has been achieved to date in unraveling the mysteries of brain operations, major research initiatives, fundamental challenges, and potentially realizable objectives. General research approaches aimed at constructing a wiring diagram of the brain (i.e., connectome), determining how the brain encodes and computes information, and whole brain simulation attempts are reviewed in terms of strategies employed and difficulties encountered. While promising advances have been made during the past 50 years due to electron microscopy, the development of new experimental methods, and the availability of computer-enabled high throughput imaging systems, brain research is still greatly encumbered by inadequate monitoring and recording capabilities. Four hypotheses relating to comprehension through the assembly of parts, formation of memories, influence of genes, and synapse formation are described as plausible explanations even though they cannot be validated at this time. By assessing the feasibility of overcoming the principal problems that beleaguer brain research in comparison with the potential benefits that can be derived from even partial achievement of the goals the author concludes that the significant investment of government funding is justified.