Recent interest in increasing rates of body weight gain in heifer calves before weaning is based on the promise of an increase in milk production during first lactation. This increase is usually realized by increasing milk or milk replacer intake, delaying the onset of rumen development. Simultaneously feeding liquids and solid feeds brings about new challenges. Macronutrient metabolism in growing calves is reviewed, combining literature from heifer and veal calves with the objective to provide insights useful for developing novel feeding strategies. Growing calves are not efficiently retaining digested N when compared with other growing species. Energy and protein appear to be simultaneously limiting growth. With the possible exception of very young calves, low responses to incremental intakes of AA indicate that the limiting AA rarely explains the low efficiency of N utilization. Nonetheless, there are indications that disproportionate oxidation of AA as a result of AA imbalance may occur, notably in splanchnic tissues. Long-chain fatty acids, absorbed from the milk or calf milk replacer (CMR) are preferentially deposited as body fat, but this strongly depends on the need for ATP, fueled by the oxidation of carbohydrates. Hence, fatty acid oxidation typically decreases with an increased feeding level. Insulin sensitivity in calves is quite high at birth, but decreases independent of feeding strategy in early age to very low levels when compared with other species. Even though changes in insulin sensitivity may be provoked by early life nutrition, these effects are small and rather transient. In heavy calves, insulin sensitivity is invariably low. Large effects of dietary treatments on postprandial glucose and insulin responses, as often observed, are unlikely to be caused by differences in insulin sensitivity. Unlike in pigs, de novo fatty acid synthesis is not a significant route of disposal of glucose absorbed from the intestinal tract. Instead, high lactate fluxes in milk-fed calves suggest this may be an important route of disposal. When combining the feeding of milk or CMR with solid feeds, estimation of the contribution of the individual ration components is difficult, and interactions inside the gastrointestinal tract complicate the estimation of their feeding value. There are indications in veal calves that use of nutrients absorbed from a CMR is not dependent on the level of intake of solid feeds.