Insulin-like growth factor-binding proteins (IGFBPs) play an integral role in modifying insulin-like growth factor (IGF) actions in a wide variety of cell types. This family contains six members that are structurally related but encoded by distinct genes. IGFBPs have a high affinity for IGFs. Some members of the IGFBP family have been consistently shown to inhibit IGF actions by preventing them from gaining access to the IGF receptors, others potentiate IGF actions by facilitating the ligand-receptor interaction. IGFBP-2 is the second most abundant IGFBP in the circulation and is present in various other biological fluids and tissues of many vertebrate species. Serum IGFBP-2 levels are elevated in many acute or chronic nonphysiological situations, such as shock, fasting, hypoxemia or after traumata, suggesting complex regulation of IGFBP-2 expression. IGFBP-2 is overexpressed in many malignancies and is often correlated with an increasingly malignant status of the tumor, pointing to a potential involvement of IGFBP-2 in tumorigenesis.