High-throughput RNA and DNA sequencing approaches continue to yield informative data that provides insights into genomic patterns and variations that influence disease susceptibility and therapy outcome in cancer. The field is currently in need of high-throughput functional assays to test the impact of genetic variations identified by these next generation genomic techniques. Such methods are essential to identify mutations and genetic patterns that drive cancer or impact response to treatment. Since a majority of diseases associated with genome instability are driven by dysfunctional DNA repair pathways, there is an urgent need for assays that can effectively characterize mutations in DNA repair genes. This review outlines salient DNA repair pathways and functional repair assays described in literature that have clinical applications.