Background Postnatal depression (PND) is common, affects the health of the mother, the development of the infant and places a large financial burden on services. Genetic and epigenetic biomarkers for PND could potentially improve the accuracy of current antenatal screening approaches. The aim of this systematic review is to report on the evidence for an association between genetic or epigenetic factors and postnatal depression. Method A systematic search of five databases (Medline, EMBASE, PILOT, PsychINFO and SCOPUS) was carried out using the following (MeSh) terms and keywords: postpartum, depression, postnatal depression, genetics, genetic polymorphisms and epigenetics. Inclusion criteria were applied and quality of studies was assessed using guidelines from the HuGE Review Handbook (Little & Higgins 2006). Results Following removal of duplicate articles, 543 remained; of these 37 met the inclusion criteria. Positive associations have been reported between PND and polymorphisms in the HMNC1, COMT, MAOT, PRKCB, ESR1, SLC6A4 genes in the presence of stressful life events, the BDNF gene when the postnatal period occurs during autumn and winter months and the OXT and OXTR genes in the presence of childhood adversity experienced by the mother. 3 Epigenetic interactions with genotype, estrogen, and childhood adversity were identified that are predictive of PND. Limitations The number of studies investigating some of the markers was small and grey literature was not included. Conclusion This review highlights the importance of examining the interaction between epigenetic, genetic, hormonal and environmental factors in order to fully understand the risk factors for PND and to improve the accuracy of current antenatal and early postnatal screening procedures. Women susceptible to PND appear to have heightened epigenetic sensitivity to the physiological changes of childbirth or to environmental factors conferred by genotype.