We present a Research Topic entitled “Somatic mutations, genome mosaicism, and aging” in Frontiers in Aging. Somatic mutations are defined as mutations that occur in cells of the body after fertilization. Since they are the root cause of essentially all cancers, somatic mutations have been extensively studied in oncogenesis. However, somatic mutations can and do occur in non-cancerous cells at any stage of embryonic development, after birth, and during aging. Somatic mutations result in genome mosaics, with cells of the same organism having distinct genome sequences. Because of this mosaicism, with most mutations unique for each individual cell, somatic mutations have been challenging to study, necessitating the development of specialized molecular and bioinformatic tools to characterize them. During aging, patterns of somatic mutation and genome mosaicism change, potentially impacting the steady decline in normal function and increase in susceptibility to disease that defines the aging process. The reviews in this collection cover a wide array of sub-topics, including the causes of somatic mutation during aging, the consequences of genome mosaicism, and the molecular and bioinformatic tools that can be used to identify somatic mutations (Table 1). In this editorial, we summarize the major themes of each review article.