The article discusses the mechanisms of copy number variation (CNV) in humans, which are major sources of genetic variation and contribute to human evolution and disease. CNVs are formed through various mechanisms, including homologous recombination (HR) and nonhomologous recombination. HR involves extensive DNA sequence identity and is crucial for accurate DNA repair, while nonhomologous recombination uses microhomology and can lead to CNVs. The article reviews models for CNV formation, emphasizing the role of nonhomologous end joining (NHEJ) and microhomology-mediated end joining (MMEJ) in repairing DNA breaks. It also discusses the breakage-fusion-bridge cycle, which can lead to chromosomal rearrangements. The article highlights the importance of CNVs in human evolution, particularly in the human and great ape lineage, and their role in diseases such as cancer. It also explores the adaptive advantages of CNVs, including gene redundancy and the potential for new functions. The article concludes that CNVs are not randomly distributed but are influenced by genomic architecture and specific chromosomal regions. The mechanisms of CNV formation are complex and involve various processes, including replication slippage, fork stalling and template switching, and microhomology-mediated break-induced replication (MMBIR). The article emphasizes the importance of understanding these mechanisms for developing therapeutic approaches to CNV-related diseases.The article discusses the mechanisms of copy number variation (CNV) in humans, which are major sources of genetic variation and contribute to human evolution and disease. CNVs are formed through various mechanisms, including homologous recombination (HR) and nonhomologous recombination. HR involves extensive DNA sequence identity and is crucial for accurate DNA repair, while nonhomologous recombination uses microhomology and can lead to CNVs. The article reviews models for CNV formation, emphasizing the role of nonhomologous end joining (NHEJ) and microhomology-mediated end joining (MMEJ) in repairing DNA breaks. It also discusses the breakage-fusion-bridge cycle, which can lead to chromosomal rearrangements. The article highlights the importance of CNVs in human evolution, particularly in the human and great ape lineage, and their role in diseases such as cancer. It also explores the adaptive advantages of CNVs, including gene redundancy and the potential for new functions. The article concludes that CNVs are not randomly distributed but are influenced by genomic architecture and specific chromosomal regions. The mechanisms of CNV formation are complex and involve various processes, including replication slippage, fork stalling and template switching, and microhomology-mediated break-induced replication (MMBIR). The article emphasizes the importance of understanding these mechanisms for developing therapeutic approaches to CNV-related diseases.