Advanced magnetic resonance imaging (MRI) techniques hold the promise to capture upper motor neuron loss and extramotor brain changes in amyotrophic lateral sclerosis (ALS) and as such deliver biomarkers relevant to diagnosis, prognosis and monitoring disease progression. However, a correlation between imaging parameters and clinical metrics has thus far been inconsistent across studies. We discuss the contributing factors to this clinical-imaging correlation gap as well as its implications for future research.