In addition to management of symptoms of disease, pharmacological interventions in adolescents with psychotic disorders must be clinically effective to provide the best possible outcome in terms of well-being, functioning, and disease burden. Six outcome domains should be considered: symptoms of disease, tolerability, everyday functioning, subjective well-being, family/career burden, and treatment adherence. To date, few studies have compared the clinical effectiveness of the different new generation antipsychotics in adolescents. However, clear differences exist between available agents, particularly in terms of tolerability profile. This review will focus on the particular issues that clinicians need to consider in order to maximise the clinical effectiveness of the new generation antipsychotics in adolescent patients with psychosis. For example, adolescents are not only more susceptible to the side effects of antipsychotic medication than adults, but they are also more likely to be sensitive to the negative impact of side effects on appearance, body image, and self-esteem. Data available in children and adolescents will be reviewed, and the practical implications for patient management will be highlighted. The importance of dosing the new generation antipsychotics appropriately will also be discussed.