Abstract: A recent study by McDonald et al. (2021) focused on how peripheral glucose metabolism and handling are compromised in amyotrophic lateral sclerosis (ALS). Dysfunctions in glucose and energy metabolism have been identified in transgenic mouse models and patients with ALS. However, how these processes are altered and contribute to disease progression are not fully understood. The aforementioned study has identified several changes to glucose homeostasis in the transgenic SOD1G93A mouse model of ALS at the later stages of the disease. Specifically, the authors found that despite insulin resistance being present, there was increased glucose uptake in ALS mice, and increased glycogen accumulation in the liver. Additionally, there was evidence of glucagon resistance developing in these mice, which supports clinical observations. This perspective outlines the key aspects of glucose metabolism and demonstrates how multiple pathways relating to these processes are compromised in ALS.