During gestation, transport by the placenta is solely responsible for nutrient supply to the developing fetus. In this context, calcium (Ca2+) transport machinery of the placenta thus represents the primary tissue site for regulating fetal Ca2+ homeostasis. In humans, the transplacental movements of Ca2+ increase dramatically during the last trimester of gestation, when fetal skeletal mineralization is at its highest. However, little is known about the exact mechanism of transport. Evidence suggests that some developmentally expressed cytosolic Ca(2+)-binding proteins (CaBPs) have an important role in regulating or shuttling cytosolic Ca2+ since they are endowed with a high affinity for Ca2+ (approximately 10(6) M(-1)). CaBPs belong to a large family of eukaryotic proteins containing a specific helix-loop-helix structure, referred to as the EF-hand motif, which counts more than 200 members. Several of these CaBPs were identified in the placenta: CaBP9k, CaBP28k, CaBP57k, oncomodulin, S-100P, S-100alpha, and S-100beta. This review discusses the current views in this field to guide future investigations into the localization and functions of CaBPs during Ca2+ intracellular homeostasis in the placenta.