Amyotrophic lateral sclerosis (ALS), the most common adult motor neuron disease, is an acquired disorder that results in loss of function in multiple domains. Although there is no treatment that can halt or reverse this progressive condition, there are many opportunities for interventions that can lead to improved quality of life for the patient and caregiver. Physical and occupational therapy can assist with mobility and activities of daily living. Interventions by speech pathology can optimize nutrition and communication. Respiratory function can be managed noninvasively or invasively. Depression, hopelessness, anxiety, and other mental health issues can and should be aggressively addressed and treated. Many symptoms such as pseudobulbar affect, sialorrhea, constipation, spasticity, and cramps can be treated effectively with medications. Spirituality and religion are important issues to address, as are end-of-life concerns, including advance directives, hospice, and the dying process. In contrast to the discouraging view that "there is nothing we can do," a broad approach to management, through collaboration with a multidisciplinary team, will permit the ALS physician to make a meaningful difference in the lives of individuals living with ALS.