This review was conducted to study the pattern of changes in the morphology of corneal nerves by in vivo confocal microscopy (IVCM) in various systemic diseases and evaluate the usefulness of this examination modality in diagnosis, treatment and prognosis of various systemic diseases. Articles were searched using the following keywords ‘Corneal nerves’, ‘sub basal plexus’, ‘confocal microscopy’, ‘corneal nerve fibre density’, ‘corneal nerve fibre length’, ‘corneal nerve branch density’, ‘cross sectional study’, ‘prospective study’, either singly or combined. Databases searched include Pubmed, Cochrane library, Embase and Science Direct. The search strategy was to include studies in which corneal nerve morphology was studied in relation to a systemic condition. 26 studies were included in this review. Changes in corneal nerve parameters were noted in systemic diseases like Diabetes Mellitus, Parkinson’s disease, Migraine etc. IVCM examination of corneal nerves has great scope as a screening tool for patients prone to develop neuropathies and also in monitoring the progression in neuropathies and certain neurological conditions.