Transient receptor potential (TRP) proteins TRPM6 and TRPM7 are α-kinase-coupled divalent cation-selective channels activated upon a reduction of cytosolic levels of Mg²⁺ and Mg·ATP. Emerging evidence indicate that one of the main physiological functions of TRPM6 and TRPM7 is maintaining of cellular metabolism of Mg²⁺ and likely other essential metals such as Ca²⁺ and Zn²⁺. Recent experiments with genetic animal models have shown that TRPM6 and TRPM7 are essential for epithelial Mg²⁺ transport in the placenta and intestine. In addition, mutations in TRPM6 or TRPM7 have been linked to Mg²⁺ deficiency in humans. However, many key functional aspects of these remarkable proteins as well as mechanisms of the associated channelopathies remain incompletely understood. The present review article highlights the recent significant progress in the field with the focus on the vital roles of TRPM7 and TRPM7 in mineral homeostasis.