Inhibitory control is an essential part of behavior. Comprehensive knowledge of the neural underpinnings will shed light on complex behavior, its breakdown in neurological and psychological disorders, and current and future techniques for the pharmacological or structural remediation of disinhibition. This study investigated the neural mechanisms involved in rapid response inhibition. The stop signal task was used to estimate inhibitory speed in a group of neurologically normal control subjects and patients with discrete frontal lobe lesions. Task procedures were controlled to rule out probable confounds related to strategic changes in task effort. The findings indicate that the frontal lobes are necessary for inhibitory control and, furthermore, that the integrity of the right superior medial frontal region is key for rapid inhibitory control under conditions controlling for strategically slow responses, forcing reliance more on a rapid, “kill-switch” inhibitory system. These results are interpreted within an anatomical framework of corticospinal motor control.