Amyotrophic lateral sclerosis is a fatal and progressive disease, characterized by progressive muscles weakness, with consequent loss of physical capacities. Patients become relentlessly immobile and, in the late stages of the disease, develop a “locked-in” state in which only residual muscular movement is possible, but the intellect and the personality usually remain unimpaired. At now, there is no cure for ALS. The psychological impact of the disease is huge, on both patients and caregivers. Aim of the present Research Topic is to collect new evidence about quality of life, depression, anxiety, pain, spiritual and existential issues, hope and hopelessness in the ALS eld, with attention to both patients and their caregivers. Emphasis will be provided to the investigation of psychological support and the possible role of psychologists in this challenging field.