Humans and other intelligent animals stand out because of the number and complexity of the associations that can be made between sensory input and behavioral responses. This flexibility depends, at least in part, on the prefrontal cortex, a region that consists of many areas that work together to produce rich, sophisticated, and even creative behaviors. These functions are not mediated by the prefrontal cortex alone, but recruit an extended network of structures with sometimes overlapping and sometimes conflicting roles. These areas acquire information about both the state of the world and the state of the body, and elicit further associations that can then be used to evaluate options, deal with conflicting possibilities, and regulate the allocation of cognitive resources accordingly. This network incorporates rapidly changing contextual information to generate an effective plan of action, inhibit unwanted or maladaptive plans, and monitor the consequences of whatever an individual ultimately chooses to do. Insults to this extended network, whether through stroke, degenerative neurological disorders, trauma or drug abuse, compromise these functions. Understanding how this mosaic of brain regions contributes to thinking, planning, and deciding is basic to understanding “higher-order” human brain functions, which is in turn needed to properly deal with a range of still poorly understood neurological and psychiatric disorders. It should be apparent from this chapter that there is still a long way to go in reaching this goal.