Cortical growth and remodeling continues from birth through youth and adolescence to stable adult levels changing slowly into senescence. There are critical periods of cortical development when specific experiences drive major synaptic rearrangements and learning that only occur during the critical period. For example, visual cortex is characterized by a critical period of plasticity involved in establishing visual acuity. Adolescence is defined by characteristic behaviors that include high levels of risk taking, exploration, novelty and sensation seeking, social interaction and play behaviors. In addition, adolescence is the final period of development of the adult during which talents, reasoning and complex adult behaviors mature. This maturation of behaviors corresponds with periods of marked changes in neurogenesis, cortical synaptic remodeling, neurotransmitter receptors and transporters, as well as major changes in hormones. Frontal cortical development is later in adolescence and likely contributes to refinement of reasoning, goal and priority setting, impulse control and evaluating long and short term rewards. Adolescent humans have high levels of binge drinking and experimentation with other drugs. This review presents findings supporting adolescence as a critical period of cortical development important for establishing life long adult characteristics that are disrupted by alcohol and drug use.