Polycystic ovary syndrome (PCOS) affects 6-20% of reproductive-aged women and is associated with various metabolic and endocrine disorders. Despite genetic studies identifying several susceptibility loci, the etiology of PCOS remains unclear. This review explores the role of epigenetic changes and modifications in circadian clock genes as potential contributors to PCOS pathogenesis. Epigenetic alterations, such as DNA methylation, histone modifications, and non-coding RNA changes, have been observed in diseases related to PCOS. Animal models have shown that prenatal exposure to androgens or anti-Müllerian hormone can induce PCOS-like phenotypes in subsequent generations, indicating epigenetic programming in PCOS. In humans, epigenetic changes have been reported in peripheral blood mononuclear cells (PBMCs), adipose tissue, granulosa cells (GCs), and liver from women with PCOS. The genome of women with PCOS is globally hypomethylated compared to healthy controls, with specific hypomethylated clusters and methylated loci identified. These changes are associated with metabolic and inflammatory pathways. Sleep disorders and disruptions in clock gene expression patterns have also been observed in PBMCs and GCs of women with PCOS. While epigenetic changes hold promise as diagnostic biomarkers, distinguishing whether they are causes or consequences of PCOS remains challenging. Targeting epigenetic modifications could open avenues for precision medicine in PCOS, including lifestyle interventions and drug therapies. However, more data are needed from large cohorts of well-characterized PCOS phenotypes. Understanding the interplay between genetics, epigenetics, and circadian rhythms may provide valuable insights for early diagnosis and therapeutic strategies in PCOS.Polycystic ovary syndrome (PCOS) affects 6-20% of reproductive-aged women and is associated with various metabolic and endocrine disorders. Despite genetic studies identifying several susceptibility loci, the etiology of PCOS remains unclear. This review explores the role of epigenetic changes and modifications in circadian clock genes as potential contributors to PCOS pathogenesis. Epigenetic alterations, such as DNA methylation, histone modifications, and non-coding RNA changes, have been observed in diseases related to PCOS. Animal models have shown that prenatal exposure to androgens or anti-Müllerian hormone can induce PCOS-like phenotypes in subsequent generations, indicating epigenetic programming in PCOS. In humans, epigenetic changes have been reported in peripheral blood mononuclear cells (PBMCs), adipose tissue, granulosa cells (GCs), and liver from women with PCOS. The genome of women with PCOS is globally hypomethylated compared to healthy controls, with specific hypomethylated clusters and methylated loci identified. These changes are associated with metabolic and inflammatory pathways. Sleep disorders and disruptions in clock gene expression patterns have also been observed in PBMCs and GCs of women with PCOS. While epigenetic changes hold promise as diagnostic biomarkers, distinguishing whether they are causes or consequences of PCOS remains challenging. Targeting epigenetic modifications could open avenues for precision medicine in PCOS, including lifestyle interventions and drug therapies. However, more data are needed from large cohorts of well-characterized PCOS phenotypes. Understanding the interplay between genetics, epigenetics, and circadian rhythms may provide valuable insights for early diagnosis and therapeutic strategies in PCOS.