The human capacity to maintain an overarching control over mental states and behavior relies on multiple, distributed and dynamically interacting brain networks, in which prefrontal cortex (PFC) plays a critical role. PFC exerts top‐down executive control over subcortical and posterior cortical areas via extensive reciprocal connections. The orbital, lateral, and medial PFC subdivisions are associated with distinct executive functions, but their precise roles in large‐scale neural networks remain to be determined. The main objective of our research program is to specify cognitive and neural mechanisms that govern executive control functions. We study effects of focal PFC lesions on behavioral and electrophysiological correlates of attention and action control utilizing experiments that relate to real‐life requirements for executive control. We provide a selective review of studies on the impact of lesions to PFC subregions on novelty processing, anticipatory attention, and action preparation and motor inhibition. The studies provide evidence for the contribution of both lateral, dorsomedial and orbital PFC in novelty processing and dynamic contextual updating. We also report evidence for a role of lateral PFC in motor preparation and anticipatory attention. In contrast to the common view that orbitofrontal cortex plays a general role in inhibitory control, we report findings indicating an involvement in action outcome monitoring rather than in behavioral inhibition as such. We argue that improved understanding of how basic aspects of attentional control and inhibition is regulated in the brain, will shed light on the complex behavioral, cognitive and emotional problems experienced by patients with executive dysfunction.