Stevens-Johnson syndrome is a severe and potentially life-threatening cutaneous reaction associated with lamotrigine. The incidence of developing Stevens-Johnson syndrome during lamotrigine therapy is low. On the basis of the glutamate and dopamine neuron dysregulation hypothesis in schizophrenia, we propose new strategies for the treatment of schizophrenic patients using a glutamate system stabilizer lamotrigine as an adjunctive treatment for the poor responders of a dopamine system stabilizer, aripiprazole. The finding of Stevens-Johnson syndrome in two cases out of three treated with lamotrigine plus aripiprazole, however, has a much higher index of suspicion and it is correct to warn of its possible raised risk. As lamotrigine is currently licensed for the prophylactic treatment of bipolar depression, many of these patients have psychotic features where it would be considered reasonable to add an antimanic atypical antipsychotic such as aripriprazole. The two case reports raised the question about the possible increased risk of Stevens-Johnson syndrome with the combination therapy.