The advent of the genome era after the completion of the Human Genome Project has resulted in intensive efforts to identify all genetic variants that modify human health and disease, including cancer. The development of genome-wide association study (GWAS) approach has facilitated this goal by unbiased examination of the entire human genome for disease association. Here, we review some of the GWAS data, particularly for bladder cancer, and assess their significance in risk prediction and prognosis. A mechanistic understanding of the risk association through functional studies and phenotypic assays is also discussed. The ultimate goal is the development of a comprehensive risk prediction model which integrates genetic, environment, and person risk factors to benefit disease diagnosis, prevention, and treatment.