The current paradigm of modern healthcare is a reactive response to patient symptoms, subsequent diagnosis and corresponding treatment of the specific disease(s). This approach is predicated on methodologies first espoused by the Cnidean School of Medicine approximately 2500 years ago. More recently escalating healthcare costs and relatively poor disease treatment outcomes have fermented a rethink in how we carry out medical practices. This has led to the emergence of “P-Medicine” in the form of Personalized and Precision Medicine. The terms are used interchangeably, but in fact there are significant differences in the way they are implemented. The former relies on an “N-of-1” model whereas the latter uses a “1-in-N” model. Personalized Medicine is still in a fledgling and evolutionary phase and there has been much debate over its current status and future prospects. A confounding factor has been the sudden development of Precision Medicine, which has currently captured the imagination of policymakers responsible for modern healthcare systems. There is some confusion over the terms Personalized versus Precision Medicine. Here we attempt to define the key differences and working definitions of each P-Medicine approach, as well as a taxonomic relationship tree. Finally, we discuss the impact of Personalized and Precision Medicine on the practice of Critical Care Medicine (CCM). Practitioners of CCM have been participating in Personalized Medicine unknowingly as it takes the protocols of sepsis, mechanical ventilation, and daily awakening trials and applies it to each individual patient. However, the immediate next step for CCM should be an active development of Precision Medicine. This developmental process should break down the silos of modern medicine and create a multidisciplinary approach between clinicians and basic/translational scientists.