Family history has been a recognized risk factor for breast cancer for many years. We will, in this review, describe the research field in breast cancer susceptibility from the early epidemiological, loss of heterozygosity (LOH), and linkage studies in the 1990s leading to the discovery of BRCA1 and 2, and the subsequent search for other high- and low-risk genes at present. We will also describe the clinical implications of BRCA1 and 2. Finally, we will give a review of the field but also focus on our own research, molecular and clinical.