Statistics is an integral part of research in ophthalmology. The application of appropriate statistical strategies allows clinicians to realize the full potential in analyzing data from paired ocular measurements, longitudinal design, and genome-wide association study (GWAS). The increasing popularity of longitudinal follow-up in either clinical or epidemiologic study demands advanced statistical methodologies. This article describes robust statistical models that can cope with correlated components for both paired-eye data and repeated measurements over time. Also highlight are the statistical challenges and corresponding strategies available for testing multiple hypotheses with paired-eye data in GWAS, which has been the subject of intense interest for the past 5 years within the ophthalmology community in investigating the genetic etiology of eye disorders.