Our collective desire to understand how the “normal” vs. “diseased” brain works drives our ongoing need for nonhuman animal research. Our current understanding of circuits within the brain, and the techniques required to investigate neural activity, stem from animal work. These techniques often require invasive methods, which necessitate animal models. Unfortunately, this means that our investigative approaches are subject to the same limitations that animal models had before these new techniques were developed. In this article I briefly overview these limitations, then outline a relatively new strategy that enables us to establish a causal relationship between a specific neurocircuit abnormality and disease. This approach utilizes novel techniques designed to selectively target mutations to specific brain circuits in the mouse. Such a strategy allows the researcher to “home in” on how a gene affects a single brain circuit. This is powerful because it avoids an often-cited problem that plagues traditional animal models: non-targeted mutations disrupt a myriad of circuits. Rather than mutating all brain cells, targeting a gene known to be highly penetrant for human disease to an individual, relatively conserved, circuit element helps us determine whether that circuit is involved in generating an abnormal behavioral phenotype. This will provide invaluable clues about where and how psychiatric disease originates in humans. Finally, I briefly discuss how computational neuroscience-based techniques and noninvasive, low-risk neuromodulation techniques could be employed to test hypotheses generated by these animal models in humans, leading to both greater understanding of neurocircuits underlying psychiatric disease and possibly new treatments.