Abstract Motor neurone disease (MND) is a disabling and ultimately fatal disease of the motor system, which unfortunately has few effective treatments. With a relatively uniform incidence worldwide of about 2 per 100,000 per year, there are approximately 5000 cases of MND in the UK at any one time. Considerable heterogeneity is observed in the clinical motor features of MND, and extra-motor manifestations are now also recognized as part of the condition. Without specific disease markers, diagnosis remains clinical, with appropriate use of investigations to exclude mimics. Patient management is challenging but can be optimized by ensuring regular specialist follow-up, open but sympathetic communication and a multidisciplinary team approach. Advances in the holistic care of patients living with MND have achieved significant improvements in the management of physical, social and psychological symptoms. Although the disease remains incurable, a survival benefit has been observed with new therapies, particularly the use of non-invasive ventilation and riluzole, now licensed for MND and recommended by NICE guidelines. The challenge to elucidate the underlying aetiology of MND and establish effective disease-modifying therapies continues through active basic science and clinical research. We provide a comprehensive review of this disease, focusing on the clinical features, diagnosis and management.