Copy number variants (CNVs) are an important source of human genomic diversity. They impact upon a diverse array of specialist fields such as evolutionary biology, predisposition to inherited disease (monogenic and complex), cancer genetics, inter-individual variation in diverse human populations, and somatic mosaicism. The important advances in CNV research that have been made over the last few years have greatly increased the awareness of the extent to which CNVs contribute to the diversity of human phenotypes, including 'single gene defects' and genomic disorders. Indeed, CNVs are now being widely investigated in genome-wide association studies to determine their influence on human disease susceptibility. This special issue comprises a unique collection of review and original articles, which together reflect the current knowledge of CNVs while posing key questions about the structure, function and evolution of this key type of polymorphic variation in the human genome. Thus it is an invaluable source of information for evolutionary biologists as well as for human and cancer geneticists.