Over 100 FDA-approved medications include pharmacogenetic biomarkers in the drug label, many with cancer indications referencing germline DNA variations. With the advent of next-generation sequencing (NGS) and its rapidly increasing uptake into cancer research and clinical practice, an enormous amount of data to inform documented gene-drug associations will be collected, which must be exploited to optimize patient benefit. This state-of-the-art article focuses on the implementation of germline cancer pharmacogenetics into clinical practice. Specifically, it discusses the importance of germline variation in cancer and the role of NGS in pharmacogenetic discovery and implementation. In the context of a scenario where massive NGS-based genetic information will be increasingly available to health stakeholders, this review explores the ongoing debate over the threshold of evidence necessary for implementation, provides an overview of recommendations in cancer by professional organizations and regulatory bodies, discusses limitations of current guidelines and strategies to improve third-party coverage
