The use of biomarkers in drug discovery and development has exploded at an unprecedented rate since the turn of the century. With recent scientific and technological breakthroughs, biomarkers can now be leveraged to address many questions about biological activity, safety, and clinical efficacy throughout the drug discovery and development process at a fraction of the cost and with turnaround times unimaginably less than a decade ago. Chad Clark et al. of Precision for Medicine identify how these advances are driving a paradigm shift in drug discovery and development.