Antidepressant response, the effectiveness of antidepressants in relieving symptoms of depression, is a complex trait influenced by both genetic and environmental factors. However, despite decades of research, the specific genetic variations that contribute to antidepressant response and treatment-resistant depression (TRD) remain largely unknown. In this review, we summarize the current state of knowledge of the genetics of antidepressant response and TRD, including candidate gene association studies, genome-wide association studies (GWAS), polygenic risk score (PRS) analyses, whole genome sequencing studies, research on other genetic and epigenetic changes, and the potential for precision medicine in this field. Although some progress has been made in identifying genetic factors associated with antidepressant response and TRD, much work remains to be done, particularly in terms of larger sample sizes and standardization of outcome measures. Further research in this area has the potential to improve the treatment of depression and increase the chances of successful treatment for individuals with this common and debilitating mental illness.