Chronic kidney disease (CKD) is a critical and rapidly growing global health problem. Neurological complications occur in almost all patients with severe CKD, potentially affecting all levels of the nervous system, from the CNS through to the PNS. Cognitive impairment, manifesting typically as a vascular dementia, develops in a considerable proportion of patients on dialysis, and improves with renal transplantation. Patients on dialysis are generally weaker, less active and have reduced exercise capacity compared with healthy individuals. Peripheral neuropathy manifests in almost all such patients, leading to weakness and disability. Better dialysis strategies and dietary modification could improve outcomes of transplantation if implemented before surgery. For patients with autonomic neuropathy, specific treatments, including sildenafil for impotence and midodrine for intradialytic hypotension, are effective and well tolerated. Exercise training programs and carnitine supplementation might be beneficial for neuromuscular complications, and restless legs syndrome in CKD responds to dopaminergic agonists and levodopa treatment. The present Review dissects the pathophysiology of neurological complications related to CKD and highlights the spectrum of therapies currently available.