Adolescence is a critical developmental period during which physical, behavioral, and neurobiological maturation occurs. Within the brain, the prefrontal cortex is one of the last brain regions to undergo remodeling, often into adulthood. These relatively late developmental changes leave the prefrontal cortex uniquely vulnerable to insults beginning in adolescence—including alcohol exposure. Adolescents initiate alcohol consumption at a high rate, increasing the risk of lasting consequences through impairing the typical development of the prefrontal cortex. In this chapter, we discuss the development of prefrontal circuitry and the current literature investigating how alcohol influences prefrontal development. We primarily focus on preclinical studies in rodent models, which allow for the study of specific populations of neurons in the prefrontal cortex. We identify several future directions for adolescent alcohol research, including greater focus on neuropeptides and stronger understanding of sex differences in brain maturation and alcohol consumption.