The genomic DNA is constantly under attack by cellular and/or environmental factors. Fortunately, the cell is armed to safeguard its genome by various mechanisms such as nucleotide excision, base excision, mismatch and DNA double-strand break repairs. While these processes maintain the integrity of the genome throughout, DNA repair occurs preferentially faster at the transcriptionally active genes. Such transcription-coupled repair phenomenon plays important roles to maintain active genome integrity, failure of which would interfere with transcription, leading to an altered gene expression (and hence cellular pathologies/diseases). Among the various DNA damages, DNA double-strand breaks are quite toxic to the cells. If DNA double-strand break occurs at the active gene, it would interfere with transcription/gene expression, thus threatening cellular viability. Such DNA double-strand breaks are found to be repaired faster at the active gene in comparison to its inactive state or the inactive gene, thus supporting the existence of a new phenomenon of transcription-coupled DNA double-strand break repair. Here, we describe the advances of this repair process.