IMPORTANCE OF THE FIELD: With the emergence of therapeutic candidates for the incurable and rapidly progressive neurodegenerative condition of amyotrophic lateral sclerosis (ALS), it will be essential to develop easily obtainable biomarkers for diagnosis, as well as monitoring, in a disease where clinical examination remains the predominant diagnostic tool. Magnetic resonance imaging (MRI) has greatly developed over the past thirty years since its initial introduction to neuroscience. With multi-modal applications, MRI is now offering exciting opportunities to develop practical biomarkers in ALS. AREAS COVERED IN THIS REVIEW: The historical application of MRI to the field of ALS, its state-of-the-art and future aspirations will be reviewed. Specifically, the significance and limitations of structural MRI to detect gross morphological tissue changes in relation to clinical presentation will be discussed. The more recent application of diffusion tensor imaging (DTI), magnetic resonance spectroscopy (MRS), functional and resting-state MRI (fMRI & R-fMRI) will be contrasted in relation to these more conventional MRI assessments. Finally, future aspirations will be sketched out in providing a more disease mechanism-based molecular MRI. WHAT THE READER WILL GAIN: This review will equip the reader with an overview of the application of MRI to ALS and illustrate its potential to develop biomarkers. This discussion is exemplified by key studies, demonstrating the strengths and limitations of each modality. The reader will gain an expert opinion on both the current and future developments of MR imaging in ALS. TAKE HOME MESSAGE: MR imaging generates potential diagnostic, prognostic and therapeutic monitoring biomarkers of ALS. The emerging fusion of structural, functional and potentially molecular imaging will improve our understanding of wider cerebral connectivity and holds the promise of biomarkers sensitive to the earliest changes.