Retinopathy of prematurity (ROP), also known as retrolental fibroplasia or a “fibroblastic overgrowth,” was the leading cause of blindness in the 1940s and 1950s. It was initially identified by physician Theodore Terry in 1942. ROP rates rapidly increased in the middle of the 1990s, especially in wealthy nations. When considering the history of conditions like ROP one sees the possible iatrogenic effects of seemingly benign therapies like giving oxygen. A review of current treatments, such as antivascular endothelial growth factor therapy, also reveals that systemic medications should be used with caution in neonates because they are still undergoing a rapid period of growth and development. This chapter reviews the history, incidence, and risk factors for development, pathophysiology, and the screening and diagnosis of ROP. It outlines the strategies to prevent ROP followed by an in-depth review of the surgical and pharmacologic treatment of this disease.