Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease that usually results in death secondary to respiratory failure. The psychological reaction to the diagnosis of ALS in patient and caregiver has received increasing attention. Reports are highly variable as to the severity of depressive symptoms in patients with ALS. When they exist, depressive symptoms can be managed with pharmacologic interventions. Recognizing cognitive impairment is essential in the management of patients with ALS. Quality of life assessments have been used to further evaluate the reaction to the disease. Maintaining a meaningful quality of life centers on psychological, supportive, and spiritual factors, as opposed to physical status. In addition to the patient's reaction, there are a variety of responses experienced by caregivers. Clinicians should provide appropriate support to the caregivers of the patients during the course of the illness and after death.