Thirty-two children (21 female and 11 male), between 7 and 14 years old, with chronic daily headache (CDH) were consecutively included in a prospective, randomized, double blind, placebo controlled crossover study. The patients were divided in group I (fluoxetine vs. placebo), with 17 patients and group II (placebo vs. fluoxetine), with 15 patients. After one month of baseline headache frequency recording, the patients received fluoxetine in dosages from 0.25 to 0.50 mg/kg for three months. A wash out period of one month was followed by another three months treatment period. Results showed a significant decrease in headache frequency in the study period [78% reduction in group I (p<0.025), and 45% reduction in group II (p=0.025)]. Gastrointestinal adverse effects were observed in nine patients (29%) that received fluoxetine, compared with 3 (10%), with placebo. We conclude that fluoxetine efficacy is not higher than placebo in the prophylaxis of CDH in children and adolescents.