Indocyanine green (ICG) is extremely effective when used as a vital stain during macular hole surgery. By staining the internal limiting membrane, ICG facilitates removal of this delicate and sometimes hard to visualize structure. There is, however, considerable debate regarding its safety. This review considers the clinical and experimental studies of ICG and a related agent, infracyanine green. Some clinical papers show visual field defects, reduced visual acuity, and persistence of ICG at the macula and optic nerve. Other clinical studies fail to demonstrate toxicity. The experimental studies are also conflicting, but there are emerging trends. These suggest that surgeons who continue to use ICG should use concentrations not greater than 0.05 mg/ml, in fluid-filled eyes, with short exposure times, iso-osmolar solutions, and avoid proximal or prolonged endoillumination of stained tissue. A smaller number of studies suggest that infracyanine green produces similar staining to ICG, and may possibly be safer, but there are too few well-designed studies to reach a conclusion. Although the use of ICG continues, on the balance of evidence, this review suggests that it is has the potential to produce subtle visual damage.