Our understanding of plus disease as an important sign for severe retinopathy of prematurity (ROP) has gradually been refined over the past 30 years. As a result of the Early Treatment for ROP (ETROP) randomized trial, the presence of plus disease is now the primary indication for laser treatment. Since the Cryotherapy for ROP trial first introduced a standard photograph as the minimum abnormality necessary for diagnosing plus disease, an intermediate level of vascular dilatation and tortuosity (pre-plus disease) has been defined. However, the recognition of plus disease remains problematic, primarily because of its subjective nature. As our understanding of the pathologic basis for plus disease in ROP grows, objective methods of recognizing and measuring retinal vascular abnormalities are also being designed. Semiautomated methods are being developed to quantify the vascular morphologic changes seen in plus disease and show promise for augmenting clinical judgment in the recognition and timely treatment of ROP.