Over the last few years, there has been a marked increase in the prescription of second-generation antipsychotics (SGA) for the treatment of psychotic disorders and other psychiatric conditions in children and adolescents. However, few reports compare the tolerability and efficacy of the different SGAs in this population. We review the literature on the differential characteristics of efficacy and tolerability of SGA in the pediatric population. Our results show that SGAs are not a homogeneous group, but that each drug has a distinct profile, particularly with respect to side effects, especially metabolic complications. Comparisons between SGAs have shown that treatment with olanzapine was associated with greater weight gain and increased cholesterol levels, and that treatment with risperidone was associated with a greater increase in prolactin levels. Therefore, the specific profile of an SGA should be taken into consideration when prescribing these drugs.