Despite an emerging link between alterations in motivated behavior and a lack of sleep, the impact of sleep deprivation as well as the potential benefit of sleep, when it is achieved, on human brain mechanisms of reward and punishment remain largely unknown. Targeting these unanswered questions, this thesis aims to determine the impact sleep loss on human brain incentive processing in topics of 1) food desire and 2) monetary gains and losses. From these investigations four main findings have emerged that make up the first four chapters of this report: 1) In the context of food choices, sleep deprivation leads to significantly decreases activity in appetitive evaluation regions within the human frontal cortex and insular cortex during food desirability choices, combined with a converse amplification of activity within the amygdala ultimately leading to increased high calorie food choices. 2) In the context of monetary rewards and losses, sleep deprivation did not lead to measurable changes in activation to the anticipation of rewards and losses in the nucleus accumbens or insula respectively. However, sleep deprivation did lead to diminished medial prefrontal cortex responses to gain outcomes and increased anterior insula response to loss outcomes. 3) Although there were no observable sleep deprivation group effects on anticipation of monetary gains and losses, there was a significant interaction of sleep deprivation with a trait dopamine transporter genetic polymorphism that determined the impact of sleep deprivation on anticipatory response to gain and loss in the nucleus accumbens and anterior insula respectively. 4) In the context of learning from monetary incentives, sleep deprivation led to a specific deficit in the ability to learn from monetary gains but no change in the learning profile for monetary losses. Finally, in addition to these four findings on the impacts of sleep deprivation on human incentive processing, the final chapter (5) focuses on the relationship between sleep, when it is achieved, and next day reward responsivity. Here there is a significant relationship between individual differences in REM sleep beta power and next day nucleus accumbens response to anticipation of rewards. Beyond these basic scientific insights, such results offer potential clinical relevance given that sleep disruption is highly co-morbid with numerous psychiatric and neurological conditions associated with dysfunctional dopaminergic reward processing (e.g., Parkinson's disease, substance abuse, and obesity). Such findings further indicate that sleep intervention may represent an under appreciated and novel therapeutic target particularly for disorders of the reward system.