Breast cancer was the first to take advantage of targeted therapy using endocrine therapy, and for up to 20% of all breast cancer patients a further significant improvement has been obtained by HER2‐targeted therapy. Greater insight in precision medicine is to some extent driven by technical and computational progress, with the first wave of a true technical advancement being the application of transcriptomic analysis. Molecular subtyping further improved our understanding of breast cancer biology and has through a new tumor classification enabled allocation of personalized treatment regimens. The next wave in technical progression must be next‐generation‐sequencing which is currently providing new and exciting results. Large‐scale sequencing data unravel novel somatic and potential targetable mutations as well as allowing the identification of new candidate genes predisposing for familial breast cancer. So far, around 15% of all breast cancer patients are genetically predisposed with most genes being factors in pathways implicated in genome maintenance. This review focuses on whole‐genome sequencing and the new possibilities that this technique, together with other high‐throughput analytic approaches, provides for a more individualized treatment course of breast cancer patients.