Long-term treatment of patients with schizophrenia is particularly difficult. An advantageous efficacy/safety profile of the selected antipsychotic is particularly important during this phase, as an insufficient response or poorly tolerated side-effects are likely to reduce compliance, notoriously poor in chronic schizophrenia patients. The atypical antipsychotic amisulpride has demonstrated good efficacy against both the positive and negative symptoms of schizophrenia in long-term clinical trials. Three studies involved treatment with amisulpride for 12 months, one in patients with positive or mixed symptoms and two in patients with predominantly negative symptoms. A further two studies, both involving patients with positive or mixed symptoms, evaluated amisulpride over periods of up to 6 months. In the three 12-month studies, amisulpride was significantly more effective than haloperidol against positive symptoms and showed a trend towards greater improvement in negative symptoms; significantly better effects compared with placebo were also seen in patients with predominantly negative symptoms. Amisulpride was well tolerated with low drop-out rates compared to standard treatment, indicating good compliance.