Presumed ocular histoplasmosis syndrome (POHS) is a significant cause of permanent visual loss primarily in the United States. This entity is also referred to as ocular histoplasmosis or presumed ocular histoplasmosis, all of which describe the same clinical scenario. The clinical findings consistent with POHS include a clear vitreous, peripapillary atrophy (PPA), peripheral punched-out chorioretinal scars and disciform macular changes. This chapter will review the epidemiology, pathogenesis, clinical features, natural history, and treatment options of POHS. The clinical features of POHS include peripapillary chorioretinal atrophy, punched-out chorioretinal lesions, disciform macular lesions secondary to CNV and a clear vitreous. These findings may be unilateral, but most often are seen bilaterally.