Electrical stimulation of the brain is an important clinical tool for treatment and diagnosis. The most visible application is therapeutic brain stimulation, such as deep brain stimulation, in which patients receive electrical pulses through implanted electrical devices to alleviate symptoms related to neurological disease. Invasive electrical brain stimulation has successfully treated patients suffering from some neurological disorders (largely movement disorders) who did not respond well to medication, markedly improving their quality of life. However, the mechanisms underlying this therapy remain mostly unknown, hindering not only the application of such technology to new neurological disorders but also the development of adaptive stimulation technologies that could improve clinical outcomes. We have begun a systematic examination of the effects of cortical electrical stimulation in human epilepsy patients. In these patients, common clinical markers of brain function and disease are recorded via typical clinical electrodes implanted on the surface of the brain. These data can uncover basic empirical principles of how electrical stimulation affects the brain. In particular, the effects of brain stimulation on local circuits have been measured in relation to the amplitude and phase of different frequencies in local field potentials. The effects of different stimulation parameters on these changes also will be quantified. In addition, functional and structural connectivity will be compared to the spatial spread of electrical stimulation effects and trial-by-trial variations in response will be used to determine how brain states can modulate the effects of electrical stimulation. Answering these questions will allow for predictions about the therapeutic effects of various stimulation paradigms, guiding clinical practice beyond trial and error.