Psychotic and negative symptoms are core features of schizophrenia but knowledge on the long-term course of these symptoms is lacking. While antipsychotics improve psychotic symptoms, they have limited effect on negative symptoms. Specialized early interventions like OPUS show great effects while ongoing but long-term follow-up indicates no lasting disease-modifying effects. 18% of patients achieved clinical recovery, and 40% obtained symptom remission after 20 years, but high mortality rates and continuous negative symptoms constitute an unmet treatment need, as argued in this review.