There are now over 28 million cancer survivors worldwide, and as a result, there is a heightened awareness of the long-term toxicities resulting from treatment and their impact on quality of life. Understanding the role of germline genetic factors in the development of cancer treatment- related toxicities is critical for the identification of patients at risk as well as for the development of drugs to treat or prevent these toxicities. The purpose of this presentation is to review current understanding of genetic susceptibility to adverse outcomes among cancer survivors following chemotherapy with a particular focus on genome-wide association studies (GWAS). Few of the findings from earlier narrowly focused candidate gene studies have been replicated in independent populations. A major strength of genome-wide approaches is that they do not require assumptions about the genes or pathways involved in the pharmacologic trait. The challenges include the need for large cohorts of patients with homogeneous treatment exposures and systematic evaluation of well-defined outcomes as well as replication in independent study populations.