ObjectivesTo examine the relationship of meaning in life (MiL) to clinical diagnosis and psychotherapy outcome and investigate specific meaning areas. Method This study investigated 214 inpatients with mental disorders and 856 healthy controls using self‐report measures of MiL and psychopathological symptoms. Results Patients showed lower MiL compared to controls. Diagnosis‐specific differences in MiL were found for depression. MiL increased in the course of treatment and remained stable at follow‐up. The most relevant meaning areas were social relationships for patients and controls. Conclusion This study provides evidence for lower MiL in inpatients with a spectrum of mental disorders, and in particular in patients with depression, compared to controls. Furthermore, perceived meaning improves over the duration of psychotherapy. Employing aspects of the meaning framework in therapy may be useful to help patients overcome psychological problems and make life worth living.