Genomic instability refers to an increased tendency of alterations in the genome during the life cycle of cells. It is a major driving force for tumorigenesis. During a cell division, genomic instability is minimized by four major mechanisms: high-fidelity DNA replication in S-phase, precise chromosome segregation in mitosis, error free repair of sporadic DNA damage, and a coordinated cell cycle progression. This introduction summarizes the major molecular processes that contribute to these mechanisms in the context of prevention of genomic instability and tumorigenesis.