Metallo-proteinases are implicated in many processes involved in tissue remodeling, cell motility, morphogenesis, and cell and organ growth and differentiation. Recent data suggest that several members of the metzincin family including the matrix metallo-proteinases (MMPs), adamalysin-related proteinases, and the newly described pappalysins, are intimately involved in the activation and/or release of cytokines and growth factors. We review how metzincins, working through unique mechanisms, influence the extracellular milieu of several important cytokines and growth factors including transforming growth factor-β (TGF-β), TNF-α, IGFs and HB-epidermal growth factor (EGF). Because metzincins can modulate the bioavailability of these peptides, they may serve as unique target molecules to control cytokine and growth factor action in the extracellular environment. © 2002 Elsevier Science Ltd. All rights reserved.