For precision medicine to become a reality, we propose three changes. First, healthcare deliverables must be prioritized, enabling translation of knowledge to the clinic. Second, physicians and patients must be convinced to participate, requiring additional infrastructure in health systems. Third, discovery science must evolve to shift the preclinical landscape for innovation. We propose a change in the fundamental relationship between basic and clinical science: rather than two distinct entities between which concepts must be translated, we envision a natural hybrid of these approaches, wherein discovery science and clinical trials coincide in the same health systems and patient populations.