The interplay between insulin-like growth factor (IGF) and insulin-like growth factor binding proteins (IGFBPs). Interactions between IGF and IGFBPs can reduce free IGF levels, decreasing insulin-like growth factor receptor (IGF-IR) activation and inhibiting cellular response. Associations of IGFBPs with extracellular matrix (ECM) components can reduce the affinity of IGFBP for IGFs, thereby releasing bioactive IGF. The actions of proteases can also increase free IGF levels, since IGFBP fragments have reduced affinity for IGFs. IGFBPs may have direct effects mediated by as yet uncharacterized IGFBP receptors.