Occurrence of keratoconus is pan-ethnic with reported prevalence ranging widely from 1:400 to about 1:8000, higher in Asian than Western populations. Its genetics is complex with undefined pattern of inheritance. Familial traits are also known. More than 50 gene loci and 200 variants are associated with keratoconus, some through association studies with quantitative traits of cornea features including curvature and central thickness. Environmental, behavioral, and epigenetic factors are also involved in the etiology, likely interactively with genetic susceptibility. Regardless of sex and age of disease onset, clinical courses and responses to treatment vary. Keratoconus is a major cause of cornea transplantation and is potentially blinding. Currently collagen cross-linking provides effective treatment although responses from some patients can be unpredictable with complications. Early diagnosis is vital to obtain good treatment outcome, but in many patients early signs and symptoms are not obvious. While there are potential biomarkers, reliable presymptomatic detection and prediction of treatment response may require multitude of gene variants, cornea properties, and external risk factors.