Postoperative pain and opioid use are major challenges in perioperative medicine. Pain perception and its response to opioid use are multi-faceted and include pharmacological, psychological, and genetic components. Precision medicine is a unique approach to individualized health care in which decisions in management are based on genetics, lifestyle, and environment of each person. Genetic variations can have an impact on the perception of pain and response to treatment. This can have an effect on pain management in both acute and chronic settings. Although there is currently not enough evidence for making recommendations about genetic testing to guide pain management in the acute care setting, there are some known polymorphisms that play a role in surgical pain and opioid-related postoperative adverse outcomes. In this review, we describe the potential use of pharmacogenomics (PGx) for improving perioperative pain management. We first review a number of genotypes that have shown correlations with pain and opioid use and then describe the importance of PGx-guided analgesic protocols and implementation of screening in a preoperative evaluation clinical setting.