During the last decade negative symptoms in schizophrenia became a legitimate indication for potential drug targets. Significant progress has been made to improve measurement of negative symptoms, to distinguish between primary and secondary negative symptoms, and the importance of predominant negative symptoms was underlined. However, few clinical trials focused on primary and/or predominant negative symptoms. A large meta-analysis found that second-generation antipsychotics (SGA) had the greatest efficacy for negative symptoms, followed by first-generation antipsychotics (FGA), combination treatments, antidepressants, and glutamatergic medications. The included studies, however, were not specifically designed to measure negative symptoms. With respect to patients with predominant negative symptoms, in the largest trial conducted so far, the SGA cariprazine was superior to its comparator, risperidone. For medication classes other than antipsychotics and antidepressants, no reliable support was found that would substantiate evidence-based recommendations for using these agents in the treatment of negative symptoms in clinical practice.