This chapter gives an overview of empirical research on and current theories of cognitive and neural mechanisms and brain systems that underlie motivated behavior and the ability to exert self-control. To this end, the chapter integrates findings from experimental psychology, cognitive neuroscience, and neuroimaging studies; studies with brain-damaged individuals; animal research; and computational models of the neurocognitive basis of motivation and self-control. Based on an analysis of fundamental adaptive challenges organisms face during the selection and control of motivated behavior, the first part of the chapter discusses neurobiological mechanisms of reward learning and incentive motivation, with a focus on behavior that is motivated by current need states and immediate reward incentives. The second part of the chapter discusses neurocognitive mechanisms underlying self-control, that is, the ability to override momentary needs or current desires in order to render one’s behavior congruent with anticipated future need states and long-term goals. The third part focuses on the interaction of motivation and cognitive control and neural mechanisms mediating effects of motivational incentives on the mobilization of cognitive control. The chapter closes with a discussion of open research questions and clinical implications.