Modern psychiatry seeks to treat disorders of the brain, the most complex and least understood organ in the human body. This complexity poses a set of challenges that make progress in psychiatric research particularly difficult, despite the development of several promising novel avenues of research. New tools that explore the neural basis of behavior have accelerated the discovery in neuroscience, yet discovery into better psychiatric treatments has not kept pace. This chapter focuses on this disconnect between the challenges and promises of psychiatric neuroscience. It highlights the need for diagnostic nosology, biomarkers, and better treatments in psychiatry, and discusses three promising conceptual advances in psychiatric neuroscience. It holds that rigorous theory is needed to address the challenges faced by psychiatrists.