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Sleep and wakefulness are complex, tightly regulated behaviors that occur in virtually all animals. With recent exciting developments in neuroscience methodologies such as optogenetics, chemogenetics, and cell-specific calcium imaging technology, researchers can advance our understanding of how discrete neuronal groups precisely modulate states of sleep and wakefulness. In this chapter, we provide an overview of key neurotransmitter systems, neurons, and circuits that regulate states of sleep and wakefulness. We also describe long-stand