Kinetic proofreading is an intrinsic property of the cell signaling process. It arises as a consequence of the multiple interactions that occur after a ligand triggers a receptor to initiate a ignaling cascade and it ensures that false signals do not propagate to completion. In order for an active signaling complex to form after a ligand binds to a cell surface receptor, a sequence of binding and phosphorylation events must occur that are rapidly reversed if the ligand dissociates from the receptor. This gives rise to a mechanism by which cells can discriminate among ligands that bind to the same receptor but form ligand-receptor complexes with different lifetimes. We review experiments designed to test for kinetic proofreading and models that exhibit kinetic proofreading.