Accurate repair of DNA double-strand breaks is essential to life. Indeed, 
defective DNA double-strand break repair can lead to toxicity and large scale 
sequence rearrangements that cause cancer and promote premature aging. Here, we 
highlight the two major repair systems for handling DNA double-strand breaks: 
homologous recombination and non-homologous end joining. To clarify 
recombination mechanisms, we present animations that illustrate DNA strand 
movements. In addition to describing how these pathways operate, we also 
describe why appropriate pathway choice is critical to genomic stability, and we 
summarize key pathway control features related to cell cycle checkpoint and 
apoptosis signaling. Importantly, recent progress in delineating the effects of 
specific defects in repair and checkpoint control has helped to explain several 
disease phenotypes, including cancer and premature aging. Improved understanding 
of these pathways has also sparked development of novel chemotherapeutic 
strategies that kill tumors with increased specificity and efficacy. This review 
aims to provide a foundational understanding of how the homologous recombination 
and non-homologous end joining pathways operate, and to demonstrate how a better 
understanding of these processes has advanced both our understanding of the 
underlying causes of cancer and our ability to innovate novel cancer treatment 
strategies.