Several epidemiological and experimental studies have demonstrated that many human diseases are not only caused by specific genetic and environmental factors but also by gene–environment interactions. Although it has been widely reported that genetic polymorphisms play a critical role in human susceptibility to cancer and other chronic disease conditions, many single nucleotide polymorphisms (SNPs) are caused by somatic mutations resulting from human exposure to environmental stressors. Scientific evidence suggests that the etiology of many chronic illnesses is caused by the joint effect between genetics and the environment. Research has also pointed out that the interactions of environmental factors with specific allelic variants highly modulate the susceptibility to diseases. Hence, many scientific discoveries on gene–environment interactions have elucidated the impact of their combined effect on the incidence and/or prevalence rate of human diseases. In this review, we provide an overview of the nature of gene–environment interactions, and discuss their role in human cancers, with special emphases on lung, colorectal, bladder, breast, ovarian, and prostate cancers.