Osteoarthritis (OA) is a heterogenous, complex disease affecting the integrity of diarthrodial joints that, despite its high prevalence worldwide, lacks effective treatment. In recent years it has been discovered that epigenetics may play an important role in OA. Our objective is to review the current knowledge of the three classical epigenetic mechanisms-DNA methylation, histone post-translational modifications (PTMs), and non-coding RNA (ncRNA) modifications, including microRNAs (miRNAs), circular RNAs (circRNAs), and long non-coding RNAs (lncRNAs)-in relation to the pathogenesis of OA and focusing on articular cartilage. The search for updated literature was carried out in the PubMed database. Evidence shows that dysregulation of numerous essential cartilage molecules is caused by aberrant epigenetic regulatory mechanisms, and it contributes to the development and progression of OA. This offers the opportunity to consider new candidates as therapeutic targets with the potential to attenuate OA or to be used as novel biomarkers of the disease.