The Senegalese sole, a species with a complex metamorphosis, difficulties in weaning and with occasional problems of malpigmentation and skeletal deformities, is a good model species to study larval nutritional physiology. In addition, the early metamorphosis and acquisition of a peculiar non-proactive bottom-feeding behaviour make early weaning an important issue in sole hatcheries. The present work reviews recent findings in different aspects of nutritional physiology during the development of Senegalese sole, in an attempt to optimize the composition of sole diets and to understand what are the limiting factors for weaning sole. Both digestive enzymes activity and tracer studies using 14C-Artemia show that sole larvae, even at young stages, have a high capacity for digesting live preys. This is reflected in a high growth potential and low mortality rates for this species during the larval stage compared to other marine fish species. Based on the observation of the digestive enzymes profile, early introduction of inert microdiets in co-feeding with Artemia does not seem to affect intestinal function. However, when co-feeding is not provided, intestinal activity may be depressed. Furthermore, early introduction of microdiets in co-feeding with Artemia may have a positive effect on survival rates, but at the expense of lower growth rates and higher size dispersal. This may reflect variation in the adaptation capacity of individual larvae to inert diets. High dietary neutral lipid (soybean oil) content results in reduced growth and accumulation of lipid droplets in the enterocytes and affects the capacity of Senegalese sole larvae to absorb and metabolise dietary fatty acids (FA) and amino acids (AA). Through tube feeding of different 14C-lipids and free FA it has been shown that FA absorption efficiency increases with unsaturation and that sole larvae spare DHA from catabolism. In addition, it was demonstrated that absorption efficiency varies according to molecular form, being highest for free FA, lowest for triacylglycerols and intermediate for phospholipids. Live preys commonly used in larviculture do not seem to have a balanced AA profile for sole larvae. Furthermore, the ideal dietary AA composition probably changes during development. Rotifers and Artemia metanauplii are apparently deficient in one or more of the following AA depending on the larval development stage: histidine, sulphur AA, lysine, aromatic AA, threonine and arginine. It has also been demonstrated that balancing the dietary AA profile with dipeptides in Artemia-fed larvae increases AA retention and reduces AA catabolism. When supplementing larval diets with limiting AA it should also be considered that sole larvae have different absorption, and retention efficiencies for individual AA, and that they have the capacity to spare indispensable AA. In addition, the absorption of free AA is faster and more efficient than that of complex proteins. Improvements in biochemical composition of inert microdiets for sole are likely to contribute to the reproducible weaning success of Senegalese sole.