Magnesium is essential for many cellular and physiological processes, including muscle contraction, neuronal activity and metabolism. Consequently, the blood Mg2+ concentration is tightly regulated by balanced intestinal Mg2+ absorption, renal Mg2+ excretion and Mg2+ storage in bone and soft tissues. In recent years, the development of novel transgenic animal models and the identification of Mendelian disorders has advanced our current insight in the molecular mechanisms of Mg2+ reabsorption in the kidney. In the proximal tubule, Mg2+ reabsorption is dependent on paracellular permeability by claudin-2/12. In the thick ascending limb of Henle's loop, claudin-16/19 provide a cation-selective pore for paracellular Mg2+ reabsorption. The paracellular Mg2+ reabsorption in this segment is regulated by the calcium-sensing receptor, PTH and mTOR signaling. In the distal convoluted tubule, the fine-tuning of Mg2+ reabsorption takes place by transcellular Mg2+ reabsorption via TRPM6/TRPM7 divalent cation channels. The activity of TRPM6/TRPM7 is dependent on hormonal regulation, metabolic activity and interacting proteins. Basolateral Mg2+ extrusion is still poorly understood, but probably dependent on the Na+ gradient. CNNM2 and SLC41A3 are the main candidates to act as Na+-Mg2+ exchangers. Consequently, disturbances of basolateral Na+/K+ transport indirectly result in impaired renal Mg2+ reabsorption in the DCT. Altogether, this review aims to provide an overview of the molecular mechanisms of Mg2+ reabsorption in the kidney, specifically focusing on transgenic mouse models and human hereditary disease.