Microcystic macular edema (MME) is the presence of small cystoid abnormalities localized in the inner nuclear layer of the retina. First identified in the context of multiple sclerosis, successive reports highlighted the presence of microcystic changes in several optic nerve conditions, such as neuromyelitis optica, optic atrophy from several etiologies, medical retinal diseases such as age-related macular degeneration and diabetic retinopathy, and in the postoperative period after epiretinal membrane peeling. Generally, these cysts are not associated with vascular leakage, unlike the more conventional types of macular edema from vascular origin. A number of theories have been proposed to explain these findings: the suspect of neuronal loss as causative finding made the hypothesis of retrograde trans-synaptic degeneration likely, more recently flanked by theories including the presence of vitreomacular traction and Müller cells dysfunction. We gather all the insights regarding the pathogenesis, epidemiology and functional impact of MME.