Morphological and physiological adaptation in residual small intestine occurs after massive enterectomy and is influenced significantly by different growth factors and hormones. The mechanism of adaptation occurs through hypertrophy and hyperplasia as well as nutrient transporter changes. These transporters are classified into different classes dependent on its biological properties. The adaptation process evolves over time and different nutrient absorption profiles occur at different postoperative stages. There is an initial decrease in amino acid transport after resection followed by a return to approximately normal levels. Glucose also follows a similar pattern of changes but returns to normal later than amino acids. The time course of these changes are different for different animals with rat adaptation being much faster than rabbit. Growth hormone (GH) induces increased amino acid transport during this adaptation period, however, appears not to affect small intestine hypertrophy or hyperplasia. The increase in transport occurs via an increase in transport numbers rather than affinity. Epidermal growth factor (EGF) also increases amino acid transport in postoperative animals. Its advantage is it is orally stable when given with a protease inhibitor. EGF also reverses the down-regulating effects of the somatostatin analogue Octreotide (SMS) post resection. EGF in combination with GH has additive effects. However, the effects of the growth factors are site specific. GH and EGF combination therapy significantly increased alanine and arginine transport in distal small bowel after 70 % enterectomy but not in the proximal small bowel. The same combination increases leucine and glutamine transport in the proximal small intestine only. Understanding the specific changes that occur with these therapies may improve quality of life for patients and also reduce that need for total parenteral nutrition.