Purpose of review Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease targeting upper and lower motor neurons, inexorably leading to an early death. Defects in energy metabolism have been associated with ALS, including weight loss, increased energy expenditure, decreased body fat mass and increased use of lipid nutrients at the expense of carbohydrates. We review here recent findings on impaired energy metabolism in ALS, and its clinical importance. Recent findings Hypothalamic atrophy, as well as alterations in hypothalamic peptides controlling energy metabolism, have been associated with metabolic derangements. Recent studies showed that mutations causing familial ALS impact various metabolic pathways, in particular mitochondrial function, and lipid and carbohydrate metabolism, which could underlie these metabolic defects in patients. Importantly, slowing weight loss, through high caloric diets, is a promising therapeutic strategy, and early clinical trials indicated that it might improve survival in at least a subset of patients. More research is needed to improve these therapeutic strategies, define pharmacological options, and refine the population of ALS patients that would benefit from these approaches. Summary Dysfunctional energy homeostasis is a major feature of ALS clinical picture and emerges as a potential therapeutic target.