Precision medicine in critical care is a key part of our present and future. However, many challenges limit its application for all patients in the ICU. Complex acute illness among patients with multi-morbidity, integrated systems biology data with daunting scope and scale, and critical illness syndromes that lack gold-standard criteria are just some of the many barriers to newer precision strategies. To move past the failures of molecularly targeted therapeutics, novel trial designs will need to embrace and explore heterogeneity of treatment during phase 2/3 evaluation. Future real-world testing and implementation of precision medicine will also require close partnership with electronic health record systems to reduce cost, improve timeliness of patient screening and treatment, and contribute to broader learning healthcare networks.

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