Current medicine is practiced in an organ-based, function-appraised manner with less attention paid to the tissue characteristics of the appraised organs. The fundamentals of this paradigm have been the product of an oversimplified and often layman-based perceptions of the studied organ over the years. These perceptions drove the current definitions of normality and abnormality, parameters used in the diagnosis of the disease, goals of treatment and studied outcomes. Despite the explosive advancement in technology that could have potentially changed our ‘upstream’ thinking, practitioners remain captives of these old beliefs and have streamlined current technology in a ‘downstream’ fashion; in the form of goal-directed protocols, and engineering systems that would study their implementations. As a result, diseases continue to evolve, become more resistant to therapy, late to diagnose, and with a persistent worsening of outcomes. With a primarily focus on the heart and from an anesthesiologist prospective, we challenge the fundamentals of the current paradigm from an ‘upstream’ prospective. We challenge the current ‘territorial’ definitions of the organs studied, the current terminology of some diseases, the parameters used in their diagnosis, the diagnostic modalities used and their goals of treatment. We illustrate some examples when the current collective ‘myth’ meets the ‘reality’ in an acute care setting, further clarifying the limitations of the current paradigm. We also, provide a theoretical hypothesis of what we believe to be a potential substitute of the current paradigm. Our theory redefines disease from an organ-based functional phenomenon to a structural-based tissue phenomenon, calling for an integrative and holistic approach of tissue assessment rather than a discrete approach that may potentially obscure the interaction of non-appraised organs. We also believe in redirecting technology in an upstream direction to better redefine and early detect diseases rather than submitting to generationally inherited beliefs. Whereas we have started some of our research on our proposed paradigm, our theoretical framework remains to be thought-provoking, and hypothesis-generating at the present time.