Nigel Leigh, PhD, MBBS, PhD, FRCP, FAAN, FMedSci, University of Sussex, Brighton, UK, discusses promising biomarker candidates in amyotrophic lateral sclerosis. Several clinical and molecular biomarkers are proposed to diagnose the disease, including neurofilaments, metabolites, TDP-43, tau, and markers of oxidative stress. Inflammatory markers are also under investigation as potential clinically useful biomarkers for ALS, such as altered cytokine and chemokine expression in blood and spinal fluid. Those studied to date have not been found to be sensitive or specific enough to have diagnostic utility. Another interesting area is microRNAs and non-coding RNAs – this has promise but has yet to yield anything specific in terms of diagnosis. Prof. Leigh notes that combining several distinct biomarkers and using big data and artificial intelligence approaches may be the best way forward. Defining a biomarker panel that accurately reflects an ALS diagnosis, can track disease progression, or predict patient outcomes is an important future goal. This is critical because ALS is a heterogeneous disorder, and therefore it is unlikely that one molecular or imaging biomarker could be proficient for every case of ALS. This interview was conducted during the 2022 World Congress on Controversies in Neurology (CONy) meeting.