Among women with breast cancer, there is wide variability in outcomes, both in treatment-related toxicities and disease-free survival (DFS). Primary predictors of DFS are those related to the extent of the disease and tumor characteristics, associated not only with tumor aggressiveness, but also responsiveness to targeted therapies. Inherited germline variation may also play a role in cancer treatment outcomes, and there have been studies targeting drug metabolism and other candidate pathways as well as genome-wide association studies (GWAS), which take a more agnostic approach and interrogate hundreds of thousands single nucleotide polymorphisms (SNPs) to determine those that modify response to breast cancer treatment. While this field of pharmacogenetics and pharmacogenomics has held exciting promise for personalized medicine, the results have not been as consistent, or the effects as profound, as first hoped. An emerging field in studies of cancer prognosis is epigenetics, which regulates DNA expression and can be influenced by numerous biologic processes as well as environmental exposures. Although young, this field of research likely holds promise for understanding of epigenetic mechanisms driving cancer and cancer outcomes, with a potential to modify these factors through drugs or other approaches. Finally, circulating markers in blood that reflect some lifestyle factors have also been studies in relation to cancer outcomes, particularly Vitamin D. In this chapter, we highlight advances in the areas noted above, and comment on factors that can impact interpretation of results from observational studies. We also discuss future directions, and avenues necessary to move the field forward.