<p>Clonal hematopoiesis (CH) — clonal expansion of hematopoietic stem or progenitor cells due to somatic mutation — is associated with increased pathogenic risk and inferior clinical outcome of multiple diseases other than hematological diseases, such as cardiovascular diseases, solid tumors, kidney diseases, chronic liver diseases, and neurodegenerative diseases, as evidenced by many cohort studies. Of note, advanced knowledge about the underlying mechanisms of how CH specifically affects these diseases, including clonal expansion and abnormal hematopoiesis, immune dysregulation, chromosome aberration, genomic instability and epigenetic regulation, which identifies novel therapeutic targets and provides important rationale for treatment strategies. Here, we focused on the pathogenic role of CH in non-hematologic diseases and comprehensively reviewed recent researches on the pathogenic mechanisms of CH to provide a systematic and global view of CH-related pathogenesis.</p>