Impulse regulation disorders and substance abuse disorders have considerable consequences for treatment and prognosis of comorbid psychiatric disorders. Second generation antipsychotics (SGA) are frequently prescribed off-label for these disorders. This off label use of SGA entails some systematic problems, such as lack of knowledge about their long-term efficacy and effects, including side-effects, and unclarity about doses in certain disorders and patient groups, for example children and adolescents. In this review we describe the evidence that supports off-label use of the second generation antipsychotics risperidone, olanzapine, clozapine, ziprasidone, quetiapine and aripiprazole in impulse regulation disorders and substance abuse disorders. We discuss these disorders together since we argue that the central feature of impulsivity in both disorders is a possible target for antipsychotic medication. Subsequently we discuss the adverse effects of these agents and we consider some hypotheses about the mechanism of action in these disorders. Several double-blind randomised placebo-controlled trials have proven that risperidone is effective in attention-deficit and disruptive behavior disorders in children and adolescents, in behavioral problems and subaverage intelligence and in tic disorders. Some double-blind randomised placebo-controlled trials, open-label studies and case reports find efficacy of olanzapine in tic disorders and pervasive developmental disorder. Risperidone and olanzapine are found to be ineffective in substance use disorders. In tic disorders two double-blind randomised placebo-controlled trials show inefficacy of clozapine and efficacy of ziprasidone. Some open-label studies found no benefit of quetiapine in pervasive developmental disorder. Single-blind and open-label studies argue the benefit of clozapine, quetiapine and aripiprazole in substance abuse and dependence. A few open-label studies and case reports suggest efficacy of quetiapine, aripiprazole and ziprasidone in attention-deficit and disruptive behavior disorders in children and adolescents and in tic disorders. Metabolic side effects such as hyperglycaemia and diabetes mellitus, weight gain and hyperlipidaemia are reported in all SGA, but especially in clozapine and olanzapine. In children they seem to be more pronounced than in adults. The most reported side effect in off-label SGA use in children, adolescents and adults is sedation. More double-blind randomised placebo-controlled trials into the long-term efficacy and safety of second generation antipsychotics are needed. Moreover head to head comparison of SGA against each other and against first-generation antipsychotic medication is still needed to determine the superiority of specific agents in treatment of specific disorders.