Disorders related to the misuse of certain drugs represent not only a worldwide public health problem, but also an economic and social issue. Adolescents and children represent the most vulnerable population for drug consumption and addiction. At this early stage in life, a crucial phase of the neurodevelopmental process, substance abuse can induce brain plasticity mechanisms that may produce long-lasting changes in neural circuitry and ultimately behavior. One of the consequences of these changes is the impairment of cognitive functions, with academic negative impact in the acquisition of new knowledge. In this chapter, we will describe the effects of illicit substances of abuse, both stimulants and depressants as well as prescription drug misuse and its influence of on learning and memory processes. Recent evidence on the new so-called smart drugs is also discussed.