•Coordinated calcium transport processes produce Ca2+ signatures in plant cells.•Magnesium transporters acquire and distribute Mg2+ throughout the plant.•CBL-CIPK signaling networks link calcium and magnesium homeostasis together. Calcium (Ca2+) and magnesium (Mg2+) are the most abundant divalent cations in plants. As a nutrient and a signaling ion, Ca2+ levels in the cell are tightly controlled by an array of channels and carriers that provide mechanistic basis for Ca2+ homeostasis and the generation of Ca2+ signals. Although a family of CorA-type Mg2+ transporters plays a key role in controlling Mg2+ homeostasis in plants, more components are yet to be identified. Ca2+ and Mg2+ appear to have antagonistic interactions in plant cells, and therefore plants depend on a homeostatic balance between Ca2+ and Mg2+ for optimal growth and development. Maintenance of such a balance in response to changing nutrient status in the soil emerges as a critical feature of plant mineral nutrition. Studies have uncovered signaling mechanisms that perceive nutrient status as a signal and regulate transport activities as adaptive responses. This ‘nutrient sensing’ network is exemplified by the Ca2+-dependent CBL (calcineurin B-like)-CIPK (CBL-interacting protein kinase) pathway that serves as a major link between environmental nutrient status and transport activities. In this review, we analyze the recent literature on Ca2+ and Mg2+ transport systems and their regulation and provide our perspectives on future research.