Serous detachment of the neurosensory retina and of the retinal pigment epithelium is a rare event in the course of systemic disease. Retinal pigment epithelial detachments usually occur in association with serous retinal detachments, although, in some cases, they also may be observed as an isolated finding. In a number of patients, the initial pigment epithelial detachment may be at the origin of a later-developing serous detachment. Diagnosis of a serous detachment still is made clinically, although optical coherence tomography recently has allowed the detection of clinically occult serous elevations of the retina. The underlying mechanisms of subretinal exudation are thought to include choroidal vascular perfusion and permeability changes, which result in increased choroidal interstitial fluid with further extension into the subretinal space. These changes are mostly incurred in the course of systemic inflammatory and infectious diseases such as sarcoidosis, Vogt-Koyanagi-Harada disease, and cytomegalovirus infection, and also in association with disorders resulting in the acute occlusion of the precapillary choroidal arterioles by fibrin-platelet thrombi. Collagen vascular diseases, disorders associated with disseminated intravascular coagulopathy, and malignant hypertension fall into this category. Hypercortisolism, renal disease, and, very rarely, malignant disease also have been implicated in the development of serous retinal detachment. Therapy of the serous detachments consists primarily of treating the underlying systemic disease.