Bladder cancer is an excellent model for studying genetic susceptibility and gene-environment interaction in cancer etiology. The candidate gene approach found NAT2 slow acetylator and GSTM1-null genotypes to be bladder cancer susceptibility loci and also demonstrated interactions between these two genotypes and smoking in modulating bladder cancer risk. Recent genome-wide association studies identified at least eight novel genetic susceptibility loci for bladder cancer. Genetic determinants of clinical outcomes have been inconclusive. The future directions are to identify more genetic susceptibility loci for bladder cancer risk and outcome through a genome-wide association study approach, identify the causal genes and variants, study the biological mechanisms underlying the association between the causal variants and bladder cancer risk, detect gene-environment interactions and incorporate genetic knowledge into clinically applicable risk prediction models to benefit patients and public health.