DNA repair is a complicated biological process consisting of several distinct pathways that play a central role in maintaining genomic stability. Research on DNA repair and cancer risk is a vital, emerging field that recently has seen rapid advances facilitated by the completion of the Human Genome Project. In this review, we described phenotypic and genotypic markers of nucleotide excision repair (NER) that have been used in molecular epidemiology studies. We summarized the population-based studies to date that have examined the association between DNA repair capacity phenotype and genetic polymorphisms of the NER genes and risk of tobacco-related cancers, including cancers of the lung, head and neck, prostate, bladder, breast, and esophagus. We also included studies of melanoma and nonmelanoma skin cancers because individuals with defective NER, such as patients with xeroderma pigmentosum (XP) are highly susceptible to ultraviolet light (UV)-induced melanoma and nonmelanoma skin cancers. The published data provide emerging evidence that DNA repair capacity may contribute to genetic susceptibility to cancers in the general population. However, many of the studies are limited in terms of the size of the study populations. Furthermore, all published findings are still considered preliminary, the assays used in the studies have yet to be validated, and the results need to be confirmed. Large and well-designed population-based studies are warranted to assess gene-gene and gene-environment interactions and to ultimately determine, which biomarkers of DNA repair capacity are useful for screening high-risk populations for primary prevention and early detection of tobacco-related cancers.