Smoking behavior is influenced by both genetic and environmental factors. Many years of twin and adoption studies have demonstrated that heritability is at least 50% for both smoking initiation and smoking persistence. Furthermore, the extent to which genetic and environmental factors contribute to smoking behavior in men is significantly different from that in women. It has been reported that polymorphisms of candidate genes, such as cytochrome P450, dopamine receptor and transporter, and serotonin transporter genes, are associated with smoking behavior. However, many of these reports have not yet received independent confirmation. Based on the results from genome-wide linkage and association analyses on different subject populations, 15 loci located on 8 chromosomes were reported to harbor susceptibility genes for nicotine and other substances of abuse. It is expected that a newly completed human genome sequence, as well as advances in genomic technologies such as genotyping and array analysis, will greatly enhance progress toward the identification of genes associated with smoking behavior.