Background and Objectives: Demoralization has been defined by hopelessness and helplessness attributable to a loss of purpose and meaning in life. Demoralization is a meaningful mental health concern, frequently associated with suicide risk in medical and psychiatric patients. The aim of this systematic review was to synthesize the recent empirical evidence on demoralization in patients with schizophrenia and to better understand the relationship between demoralization and suicide risk in patients with schizophrenia. Methods: A comprehensive literature search using key words and subject headings was performed following PRISMA guidelines with several bibliographic databases, resulting in the identification of 27 studies. Results: The findings suggested that demoralization is prevalent in patients with schizophrenia and supported the hypothesis that the association between depression and suicide is moderated by hopelessness. In clinical practice, it is important to recognize symptoms of demoralization using appropriate psychological tools to better understand the suffering of patients with schizophrenia and to implement suicide prevention programs.