Personalized medicine has typically referred to the use of genomics in clinical care. However, the concept more broadly refers to recognizing the heterogeneity of each individual patient, particularly their unique risk factors for developing disease or having poor outcomes, and using this to inform treatment decisions. Pharmacogenomics was perhaps the first major clinical application that came out of the Human Genome Project, but its translation to the critical care arena has been limited by numerous factors. Biomarkers have been widely studied in critical illnesses such as sepsis and acute respiratory distress syndrome in an attempt to aid in accurate diagnostic classification, to predict outcomes, and to assess response to therapy. Clinical use of such biomarkers has remained limited, but multi-biomarker panels have attempted to better reflect the complex physiology of critical illness, and to assist in design and recruitment for clinical trials. Genetic association and gene expression studies have been aimed at classifying risk for and severity in disease, as well as in predicting outcomes. While our understanding of the pathogenesis of critical illness has progressed significantly, the clinical utility of genetic markers remains limited. Novel methods are reaching closer to clinically applicable platforms, both for use in clinical trials and in direct patient care. Although we are not yet living in an era of personalized and precise medical care in the intensive care unit, the future is promising.