Migraine is a common and disabling disorder, affecting children, adolescents, and adults. Prophylactic therapy should be considered when specific clinical conditions are fulfilled. Its goal is to reduce the frequency and duration of the attacks as well as the severity of pain, thus allowing patients to regain routine activities and ameliorating their quality of life. Using the principles of evidence-based medicine, a review of available published data on the efficacy and safety of prophylactic treatments for migraine in children and adolescents is presented. Currently, only flunarizine and psychologically based interventions (e.g., relaxation training, biofeedback, and psychotherapeutic techniques) may be effective in migraine prophylaxis in children and adolescents. Owing to the paucity of evidence, there is a need for large, controlled, randomized, and masked trials. Clinical researchers should consider that migraine, especially in childhood and adolescence, is a complex condition, resulting from the interaction between biological, psychological, and environmental factors. Specific events, constitutional predisposition, individual and environmental-emotional dynamics can play a significant role in the genesis and evolution of pain. Age-related characteristics such as prevalence, diagnosis, quality of life, and therapy should be considered designing future studies. Drug Dev Res 68: 461-468, 2007.