Components of human executive function, like rule generation and selection in response to stimuli (attention set-shifting) or overcoming a habit (reversal learning), can be reliably modelled in rodents. The rodent paradigms are based upon tasks that assess cognitive flexibility in clinical populations and have been effective in distinguishing the neurobiological substrates and the underlying neurotransmitter systems relevant to executive function. A review of the literature on the attentional set-shifting task highlights a prominent role for the medial region of the prefrontal cortex in the ability to adapt to a new rule (extradimensional shift) while the orbitofrontal cortex has been associated with the reversal learning component of the task. In other paradigms specifically developed to examine reversal learning in rodents, the orbitofrontal cortex also plays a prominent role. Modulation of dopamine, serotonin, and glutamatergic receptors can disrupt executive function, a feature commonly exploited to develop concepts underlying psychiatric disorders. While these paradigms do have excellent translational construct validity, they have been less effective as predictive preclinical models for cognitive enhancers, especially for cognition in health subjects. Accordingly, a more diverse battery of tasks may be necessary to model normal human executive function in the rodent for drug development.