Antidepressant medications are frequently used as the first line of treatment for depression. However, their effectiveness is highly variable and influenced by genetic factors. Recently, pharmacogenetic studies, including candidate-gene, genome-wide association studies or polygenic risk scores, have attempted to uncover the genetic architecture of antidepressant response. Genetic variants in at least 27 genes are linked to antidepressant treatment response in both coding and non-coding genomic regions, but evidence is largely inconclusive due to the high polygenicity of the trait and limited cohort sizes in published studies. Future studies should increase the number and diversity of participants to yield sufficient statistical power to characterize the genetic underpinnings and biological mechanisms of treatment response, improve results generalizability and reduce racial health-related inequities.