A central tenet of modern neuroscience is the conceptualization of the brain as a collection of complex networks or circuits with a shift away from traditional “localizationist” theories. Connectomics seeks to unravel these brain networks and their role in the pathophysiology of neurologic diseases. This article discusses the science of connectomics with the examples of its potential role in clinical medicine and neuromodulation in multiple disorders, such as essential tremor, Parkinson’s disease, obsessive-compulsive disorder, and epilepsy.