Human cells accumulate at least 10,000 DNA lesions every day. Failure to repair such lesions can lead to mutations, genomic instability, or cell death. Among the various types of damage which can be expressed in a cell, DNA double-strand breaks (DSBs) represent the most serious threat. Different kinds of physical, chemical, and biological factors have been reported to induce DNA lesions, including DSBs. The aim of this review is to provide a basic understanding and overview of how DSBs are produced, recognized and repaired, and to describe the role of some of the genes and proteins involved in DSB repair.