Modulation of platelet-surface activation is important for many biomedical applications such as in vivo performance, platelet storage, and acceptance of an implant. Reducing platelet-surface activation is challenging because they become activated immediately after short contact with nonphysiological surfaces. To date, controversies and open questions in the field of platelet-surface activation still remain. Here, we review state-of-the-art approaches in inhibiting platelet-surface activation, mainly focusing on modification, patterning, and methodologies for characterization of the surfaces. As a future perspective, we discuss how the combination of biochemical and physiochemical strategies together with the topographical modulations would assist in the search for an ideal nonthrombogenic surface.