Postpartum depression (PPD) is a serious mood disorder that may carry life-long consequences for a woman and her family. Multiple risk factors for PPD have been identified, including psychosocial, situational, and biological stimuli, several of which are experienced by most, if not all, postpartum women. Given the commonality of these risk factors, it is unclear why fewer than 20% of postpartum women actually develop PPD. In this review, we suggest that different susceptibility to PPD among postpartum women may be explained by the presence or absence of genetic variants that confer increased risk. We review three categories of genes known to code for proteins associated with depression in the general population or proteins known to be affected by childbirth for their possible association with PPD, including genes related to central nervous system monoamine availability, proinflammatory cytokines, and brain neuropeptides. Only two studies are available in the literature to date specifically looking at polymorphisms in postpartum women as related to PPD; both are concerned with monoamine availability. These are discussed in further depth. Conclusions regarding the contribution of genetic polymorphisms to the development of PPD are mixed. Ultimately, the complexity of the disorder and the interrelationships among different genes thought to contribute to depression suggest that much more research is required to understand the heritability of PPD. The complexity of the disorder also suggests that epigenetic influences must be considered as well when discussing susceptibility.