The presence of breast cancer in first and second-degree relative increases the risk for a proband and the risk gradually rises with the number of affected relatives. Almost 20 years after BRCA1/2 discovery, other moderate-to-high penetrance susceptibility genes for breast cancer are identified, including PTEN, TP53, STK11, CDH1, PALB2, CHEK2, ATM, MRE11, RAD50, NBS1, BRIP1, FANCM, RAD51, RAD51B, RAD51C, RAD51D, and XRCC2. Since technology of next-generation sequencing may enable to simultaneously sequence of a large number of target genes, gene panel sequencing is now considered and revolutionizing germline risk assessment for hereditary breast cancer. Targeted organ screenings and prophylactic surgery are suggested to mutation carriers for avoiding advanced malignant diseases and reduce the cancer-related mortality. In addition, the majority of breast cancer-susceptibility genes are involved in critical processes of DNA repair pathways; the genetic information can provides therapeutic options, indicating sensitive response to platinum and PARP inhibitors.