Prosocial behavior refers to positive interactions with others, including helping, sharing, cooperating and comforting. Such social interactions are relevant to a variety of psychosocial adjustment outcomes, such as academic performance, depression and externalizing disorders. There is growing evidence for the importance of genes and its interactions with environmental factors in the development of prosocial behavior. In particular, a genetic polymorphism in the exon III repeat region of the dopamine receptor D4 (DRD4) gene has been the focus of interest regarding prosocial behavior. Specifically, the existing research has examined direct effect of DRD4 gene on prosocial behavior and found that 4R allele carriers exhibited more prosocial behavior compares to other genotype carriers. Studies regarding empathy has provided supports for the association between DRD4 gene and prosocial behavior, and further implied potential gender differences in these associations. Notably, given the lack of relevant studies, what is less well understood are the gender difference in the relationship between DRD4 and prosocial behavior. Moreover importantly, DRD4 genes often interact with environment factors in their effects on prosocial behavior. However, mixed findings were obtained. Some studies found that the interactions between DRD4 and family environment were significantly associated with prosocial behavior. Specifically, children with 7R alleles experiencing positive family environment reported higher levels of prosocial behavior but reported less prosocial behavior when experiencing negative family environment. But these effects were not confirmed in other studies assessing peer environmental factors. One possibility is that the vulnerability of DRD4 gene may vary across developmental periods. Besides, researchers also examine the interaction of distal environmental factors such as religion and the birth season and the DRD4 gene VNTR polymorphism on children’s prosocial behavior. Consistent with results from gene by family factor interactions, individuals with low activity alleles were more sensitive to environments. The interaction between DRD4 and environment on prosocial behavior have been commonly discussed, but the underlying mechanisms that why the G × E interaction influence prosocial behavior remains unclear. The gene-brain-behavior framework and neurobiological evidence suggest that specific brain regions implicated in emotional process and reward pathway may mediated the associations between DRD4 and prosocial behaviors. The existing body of genetic studies on prosocial behavior implied that the DRD4 gene is implicated in the development of prosocial behavior. But gaps remain in furthering the understanding of mixed results and the mechanism why the G × E operates to influence prosocial behavior. Therefore, future studies should focus on: (a) testing the dynamic changes in gene-environment interactions over development; (b) exploring the gender difference in the association between DRD4 and prosocial behavior; (c) recognizing the multifaceted nature of prosocial behavior by conducting multitrait–multimethod studies; (d) investigating the underlying neurobiological mechanisms between DRD4 gene and prosocial behavior.