Amyotrophic lateral sclerosis is a fatal neurodegenerative disease with a progressive and rapid course that, so far, cannot be stopped or reversed. The psychological impact of the disease is huge, on both patients and caregivers. This review summarizes studies that have investigated quality of life, depression, anxiety, pain, spiritual and existential issues, hope, and hopelessness in the ALS field, with attention to both patients and their caregivers. Psychological support and the possible role of psychologists in the ALS field are also discussed.