As in other areas of medicine, the specialty of critical care medicine, which has made important contributions in the pathophysiology of critical illness, is facing challenges that must be recognized and addressed in the current century. In this review, we argue that the skill set required to adequately treat critically ill patients will also require knowledge of molecular biology for better diagnosis and treatment. The foundations of molecular biology and genetics are essential for the understanding of the mechanisms of disease. Incorporating molecular biology techniques in the research arsenal of the intensivist will provide the opportunity to dissect out and define the reversible and irreversible intracellular processes giving rise to the major causes of mortality in intensive care units. Two historical paradigms, the cardiopulmonary resuscitation and polymerase chain reaction, summarize how critical care medicine began, and how it could mature in the years to come.