Intestinal Ca2+ absorption is a crucial physiological process for maintaining bone mineralization and Ca2+ homeostasis. It occurs through the transcellular and paracellular pathways. The first route comprises 3steps: the entrance of Ca2+ across the brush border membranes(BBM) of enterocytes through epithelial Ca2+ channels TRPV6, TRPV5, and Cav1.3; Ca2+ movement from the BBM to the basolateral membranes by binding proteins with high Ca2+ affinity(such as CB9k); and Ca2+ extrusion into the blood. Plasma membrane Ca2+ ATPase(PMCA1b) and sodium calcium exchanger(NCX1) are mainly involved in the exit of Ca2+ from enterocytes. A novel molecule, the 4.1R protein, seems to be a partner of PMCA1 b, since both molecules colocalize and interact. The paracellular pathway consists of Ca2+ transport through transmembrane proteins of tight junction structures, such as claudins 2, 12, and 15. There is evidence of crosstalk between the transcellular and paracellular pathways in intestinal Ca2+ transport. When intestinal oxidative stress is triggered, there is a decrease in the expression of several molecules of both pathways that inhibit intestinal Ca2+ absorption. Normalization of redox status in the intestine with drugs such as quercetin, ursodeoxycholic acid, or melatonin return intestinal Ca2+ transport to control values. Calcitriol [1,25(OH)2D3] is the major controlling hormone of intestinal Ca2+ transport. It increases the gene and protein expression of most of the molecules involved in both pathways. PTH, thyroid hormones, estrogens, p ro l a c t i n, g ro w t h h o r m o n e, a n d g l u c o c o r t i c o i d s apparently also regulate Ca2+ transport by direct action, indirect mechanism mediated by the increase of renal 1,25(OH)2D3 production, or both. Different physiological conditions, such as growth, pregnancy, lactation, and aging, adjust intestinal Ca2+ absorption according to Ca2+ demands. Better knowledge of the molecular details of intestinal Ca2+ absorption could lead to the development of nutritional and medical strategies for optimizing the efficiency of intestinal Ca2+ absorption and preventing osteoporosis and other pathologies related to Ca2+ metabolism. The first route includes 3 steps: the entrance of Ca2 + across the brush border membranes (BBM) of enterocytes through epithelial Ca2 + channels TRPV6 , Ca2 + movement from the BBM to the basolateral membranes by binding proteins with high Ca2 + affinity (such as CB9k); and Ca2 + extrusion into the blood. Plasma membrane Ca2 + ATPase (PMCA1b) and sodium calcium exchanger (NCX1 ) are mainly involved in the exit of Ca2 + from enterocytes. A novel molecule, the 4.1R protein, seems to be a partner of PMCA1 b, since both molecules colocalize and interact. The paracellular pathway consists of Ca2 + transport through transmembrane proteins of tight junction structures, such as claudins 2, 12, and 15. There is evidence of crosstalk between the transcellular and paracellular pathways in intestinal Ca2 + transpo When intestinal oxidative stress is triggered, there is a decrease in the expression of several molecules of both pathways that inhibit intestinal Ca2 + absorption. Normalization of redox status in the intestine with drugs such as quercetin, ursodeoxycholic acid, or melatonin return intestinal Ca2 + transport to control values. Calcitriol [1,25 (OH) 2D3] is the major controlling hormone of intestinal Ca2 + transport. It increases the gene and protein expression of most of the molecules involved in both pathways. PTH, thyroid hormones, estrogens, p ro lactin, g ro wthhormone, and glucocorticoids apparently also regulate Ca2 + transport by direct action, indirect mechanism mediated by the increase of renal 1,25 (OH) 2D3 production, or both. Different physiological conditions, such as growth, pregnancy, lactation, and aging , adjust intestinal Ca2 + absorption according to Ca2 + demands. Better knowledge of the molecular details of intestinal Ca2 + absorption could lead to the development of nutritional and medical strategies for optimizing the efficiency of intestinal Ca2 + absorption and preventing osteoporosis and other pathologies related to Ca2 + metabolism.