Total parenteral nutrition as practiced today was not a part of modern medicine until the late 1960s. Having demonstrated that normal growth of puppies could be achieved solely with parenterally administered nutrients, Dudrick et al. adapted the technique used in animals for clinical use. Shortly thereafter, Wilmore and Dudrick described use of this new technique in treatment of an infant who had virtually no remaining small intestine and, therefore, was totally dependent upon parenterally delivered nutrients. Although the infant eventually succumbed, normal growth and development was maintained for several months solely with parenterally delivered nutrients.

This successful attempt to deliver sufficient nutrients parenterally was preceded by centuries of unsuccessful attempts beginning shortly after description of the circulatory system in the early seventeenth century and the realization that ingested nutrients reached the circulation. These attempts included infusion of wine, ale, olive oil, and milk. As easily predicted today, most were disasters. However, two of three patients who received milk infusions for treatment of cholera in the early 1800s survived but whether this was because of, or despite, the milk infusions is not clear. Since the practice was not continued, the latter seems more likely.

By the late 1800s the potentially deleterious effects of catabolism and starvation were recognized, rekindling interest in ability to provide nutrients parenterally. This resulted in development of products that could be delivered parenterally and, by the early 1940s, glucose and protein hydrolysates that could be delivered safely by the parenteral route were available.