As cows eat more feed to support higher milk production, the proportion of digested energy that is captured in milk increases. In contrast, as cows consume more feed, digestive efficiency decreases, but the magnitude of depression in digestibility is not characterized for high producing cows. Despite the digestibility depression, biological efficiency increases considerably as Holstein cows produce more milk up to 15,000 kg/yr. Above 15,000 kg/yr, the gain in biological efficiency per unit of increase in milk production is expected to approach 0. At 21,000 kg of milk/yr, similar to 25% of the gross energy consumed by the cow during the first 5 yr of life likely would be captured as milk, conceptus, or body tissues; further gains in biological efficiency are not likely without major advances in feed digestion. Although feeds generally cost more as cows are fed for higher milk production, increased productivity also enhances profitability, partly because of increased efficiency but also because fixed costs are decreased relative to total costs. This relationship between productivity and profitability is expected to continue up to > 21,000 kg/yr per cow. Other issues related to the efficiency of nutrient use will become more important in the future, namely, efficiency of the use of feeds that can also be consumed by humans, efficiency of use of tillable land, and minimization of nutrient losses to the environment.