Human milk banking was virtually discontinued at the start of the human immunodeficiency virus era amid fears that the virus might be transmitted to preterm infants receiving donor milk. However, the demand for donor breastmilk has continued to be driven by decades of research that have increasingly demonstrated the benefits of breastmilk in neonatal care regarding the reduction of lifethreatening necrotizing enterocolitis (NEC) and infection, as well as improving long-term outcomes, notably neurodevelopment and bone health. Despite the progressive return of milk banking during the past two decades, the demand for breastmilk has not been met. Now, this problem has been greatly compounded by a recent, radical increase in demand for human donor milk resulting from compelling new research that is changing the standards for how preterm infants are fed. This new research is rooted in the concept of ‘‘lactoengineering,’’ using human milk components to produce formulations and fortifiers designed to meet the special nutritional needs of preterm infants. This concept was introduced by Lucas et al. in 1980 and more recently commercialized to produce a human milk-based fortifier designed for use in the neonatal intensive care unit. The production and use of such ‘‘lactoengineered’’ products in the United States have facilitated randomized clinical trial comparisons to be made between extremely premature infants fed on human milk plus cows’ milk-based fortifier or cows’ milk-based products alone, compared with a diet that is solely based on human milk, completely excluding exposure to cows’ milk. Published clinical trial evidence has shown that such an exclusively human milk-based diet results in a major reduction in NEC, a dramatic reduction in surgical NEC, a significant reduction in mortality, and a reduction in the duration of potentially hazardous parenteral nutrition. Apart from the demonstration of such important health benefits of an exclusively human milk-based diet, the estimated health economic benefits are large, with potential savings of billions of dollars in the United States each year. But, these benefits are only possible if the supply of donor milk increases to the level required to provide a higher protein density that forms the basis for the new lactoengineered products. The availability of donor milk has diminished to the point that milk banks cannot even serve the demands of the small percentage of hospitals using donor milk. Lack of awareness, low breastfeeding rates, and the diversion of donor milk to informal milk sharing programs have been cited as the root cause of the donor milk shortage. It has also been suggested that the responsibility for increasing the supply of donor milk rests with healthcare professionals who should compel their patients to donate breastmilk. No credible evidence has been presented to support that case, and, surprisingly, there seems to be no clear plan to solve the current shortage. General statements about encouraging breastfeeding, increasing breastfeeding rates, and the societal responsibility to ensure that nursing mothers donate milk have been put forth as a solution for years, yet the current milk banking systems continue to provide only a small percentage of the donor milk needed for the most vulnerable infants. It is time for a radically different approach if we are to see this problem solved in our lifetimes. More importantly, how many lives must be lost in neonatal units before a different approach is supported? A global perspective on the availability of donor milk is even more sobering. A recent report on global prematurity states that there are 15 million preterm infants born each year. If we can’t provide an adequate supply of donor milk in the United States for a mere 67,000 preterm babies, how can we expect countries with significant constraints on resources to do so?