The neural correlates of motor execution in Amyotrophic Lateral Sclerosis (ALS) are challenging to investigate due to muscle weakness. Alternatives to traditional motor execution paradigms are therefore of great interest. This study tested the hypothesis that patients with Amyotrophic Lateral Sclerosis (ALS) would show increased cortical activation during motor imagery compared to healthy controls, as seen in studies of motor execution. Functional MRI was used to measure activation during a block design paradigm contrasting imagery of right hand movements against rest in 16 patients with ALS and 17 age-matched healthy controls. Patients with ALS showed reduced activation during motor imagery in the left inferior parietal lobule, and in the anterior cingulate gyrus and medial pre-frontal cortex. This reduction in cortical activation during motor imagery contrasts with the pattern seen during motor execution. This may represent the disruption of normal motor imagery networks by ALS pathology outside the primary motor cortex.