The thalassemias are the most common single gene disorder in the world. Over the last years, several reports have demonstrated neurological complications in beta-thalassemia patients. In most cases, these complications remained subclinical and were detected only during neuropsychological, neurophysiological, or neuroimaging evaluation. Cognitive impairment, abnormal findings on evoked potentials, complications due to extramedullary hematopoiesis, cerebrovascular disease, and peripheral neuropathy comprise the broad spectrum of neurological involvement. Chronic hypoxia, iron overload, desferrioxamine neurotoxicity, and bone marrow expansion are implicated, but sufficient explanatory evidence is lacking and development of biomarkers is needed. This review summarizes current knowledge of the neurological complications. As life expectancy for beta-thalassemia patients increases, we support the use of neurophysiological, neuropsychological, or neuroimaging monitoring, enabling the evaluation of neural pathway impairment, to achieve appropriate management and as a result a better quality of life for this patient group.