This case report deals with the antipsychotic treatment in multiple sclerosis (MS). Psychiatric symptoms are a frequent event in patients with MS. However, there are only few systematic studies of antipsychotic treatment in MS patients. Most of the studies are related to clozapine due to the lack of neurological, particularly extrapyramidal side effects (EPS). Therefore, experiences with other atypical drugs are requested. This paper discusses the pros and cons of different atypical drugs using the example of one patient, who showed adverse effects after treatment with quetiapine and olanzapine. Risperidone was not administered with respect to possible EPS. However, ziprasidone was tolerated well and appeared to be effective.