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Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that mainly affects the motor system, resulting in progressive weakness and muscle wasting. Despite the tremendous advances in physiopathological and clinical characterization, we do not have a curative treatment yet. The progressive and fatal course of ALS makes its management particularly complex and challenging given the diversity of symptoms presenting during the disease progression. The main goal in the treatment of ALS patients is to minimize morbidity and maximize the quality of life. Currently, a series of therapeutic interventions improve the quality of life and prolong survival, including multidisciplinary care, respiratory management, and disease-modifying therapy. Within the supportive interventions, weight maintenance through nutritional and metabolic support is critical. In addition, the management of neuropsychiatric manifestations and preservation of communicative capacity before speech loss are also crucial. Lastly, early palliative care intervention is essential to optimize symptomatic management. Anticipatory guidelines to face the inevitable patient deterioration should be devised. This article updates the main therapeutic strategies used in these patients, including evolving clinical trials with promising novel therapies.