Human RecQ helicases, including the Werner syndrome helicase, participate in maintaining the integrity of the genome by suppressing illegitimate recombination or by repair of local DNA structural damage. Deterioration or loss of RecQ helicase associated with aging or genetic disorder results in genomic instability in tissues and organs where certain RecQ helicases are needed to correct aberrant DNA during proliferation. Such genomic instability, if not corrected, causes increased apoptotic cell death that would result in reduction of cell numbers in some tissues, leading to the deterioration of tissues and organs, the phenotypes of aging. Besides being associated with aging, genomic instability increases the risk of the development of neoplasms, both benign and malignant. These neoplasms are produced if either a checkpoint system or apoptosis is not functioning appropriately. Malignant tumor cells would then be selected from the mixed population of neoplasms by acquiring phenotypes that permit rapid cell growth and a strong capability to maintain their genome, such as tumor cells having increased levels of RecQ helicase expression, as we have observed in various tumor cell lines. Further studies are needed to discover effective measures to control genomic instability and to manage malignant tumor cells.