Over recent years, the study of magnesium homeostasis has greatly benefited from molecular genetic approaches that identified several new classes of magnesium transporters. These proteins demonstrate a diversity of structural properties and biophysical functions that often translate into a wide range of tissue-specific cellular activities. Among these novel channels, MagT1 has gained most of the attention, given its high selectivity for Mg(2+) and its possible involvement in cellular functions reaching far beyond magnesium homeostasis, as the latest findings seem to imply. Indeed, a signaling role for MagT1 has been proven in T lymphocytes, where Mg(2+) functions as a second messenger, coupling TCR activation to intracellular effectors. We herein review these intriguing results and discuss their potential implications for magnesium research, and ultimately for therapeutic opportunities. As our knowledge of magnesium advances, it becomes increasingly clear that a deeper understanding of magnesium homeostasis is the key for a deeper insight into relevant pathophysiological conditions, and their treatment.