Gastric cancer remains the second most frequent cause of cancer-related mortality. While surgery is traditionally the initial treatment for early-stage disease, the addition of chemotherapy has been shown to significantly increase overall survival and progression-free survival in advanced and metastatic stages of disease. However, despite the incorporation of newer chemotherapies and regimens into gastric cancer clinical trials, the response rate and median overall survival for treated patients has not significantly improved throughout the years; therefore, newer therapeutic approaches to improve upon the medication selection process are warranted. Treatment and dose selection based on patient factors, such as genetic variation, may provide a more rational and potentially more powerful means of personalizing chemotherapy. This review provides an update on the current status of pharmacogenetic studies regarding germline DNA mutations that may alter response to chemotherapeutic agents used to treat gastric cancer, including perspectives on clinical translation and future work.