•Mitochondrial dysfunction is one of the earliest pathophysiological events in amyotrophic lateral sclerosis (ALS).•ALS-associated mutant proteins accumulate in mitochondria and cause mitochondrial damage.•ALS-associated mitochondrial dysfunction occurs at multiple levels.•ALS affects mitochondrial respiration and ATP production, calcium handling, dynamics, and apoptotic signalling. Mitochondria are unique organelles that are essential for a variety of cellular processes including energy metabolism, calcium homeostasis, lipid biosynthesis, and apoptosis. Mitochondrial dysfunction is a prevalent feature of many neurodegenerative diseases including motor neuron disorders such as amyotrophic lateral sclerosis (ALS). Disruption of mitochondrial structure, dynamics, bioenergetics and calcium buffering has been extensively reported in ALS patients and model systems and has been suggested to be directly involved in disease pathogenesis. Here we review the alterations in mitochondrial parameters in ALS and examine the common pathways to dysfunction.