DNA repair is an important defense mechanism that faces the difficult task of protecting the genome from the constant assaults caused by endogenous and exogenous agents. Since DNA repair mechanisms are responsible for correcting DNA damage and preserving genomic integrity, it is obvious that abnormalities of these mechanisms may result in neoplastic transformation. Hematological malignancies are characterized by genomic instability that is possibly related to underlying defects in DNA repair. The purpose of this review is to summarize the existing knowledge concerning abnormalities in DNA repair components and their influence on common hematological malignancies.