In this thesis, we examine the functionality of two platelet collagen receptors, GPVI and α2β1, in their role in platelet collagen interactions as a result of vascular injury. Using rat basophilic leukemia cells transfected with the GPVI receptor, we show that GPVI is capable of mediating adhesion to collagen under shear stress in a density-dependent fashion that is independent of signaling. To extend these findings to a more physiological context, we used pharmacologic and genetic approaches to study human and mouse platelet adhesion to collagen under arterial shear rates. Our studies demonstrate that both GPVI and integrin α2β1 play significant roles for platelet adhesion to collagen under flow, and that the loss of both receptors completely ablates this response. Intracellular signaling mediated by the cytoplasmic adaptor SLP-76, but not by the transmembrane adaptor LAT, is critical for platelet adhesion to collagen under flow. In addition, reduced GPVI receptor density results in severe defects in platelet adhesion to collagen under flow. Defective adhesion to collagen under flow is associated with prolonged tail bleeding times in mice lacking one or both collagen receptors. These studies establish platelet collagen responses under physiologic flow as the consequence of a close partnership between two structurally distinct receptors and suggest that GPVI and α2β1 play significant hemostatic roles in vivo. With the establishment that integrin α2β1 is required for platelet collagen responses, we next address how it mediates bidirectional signaling in those responses. Specifically, we study whether or not the tyrosine residues of its β1 cytoplamic domain contribute to the response in outside-in signaling by inducing mutations, YF and YA, in the NPXY motifs. We find that YF mutant platelets maintain a near normal response in platelet adhesion and spreading on collagen but the YA results show a defective response. These results suggest that the tyrosine residues are important regulators of outside-in signaling; however, tyrosine phosphorylation is not required