Platelets are anucleated fragments produced by megakaryocytes that circulate in the blood. Platelets are involved in the initial cellular response to damaged endothelium and migrate to this area to prevent excessive bleeding. What is becoming more acknowledged over the last few decades is that blood flow (hemodynamics) plays a critical role in platelet function. The purpose of this review is to summarize the current understanding of platelet biology with particular focus on the role of hemodynamics. The emerging concept of shear microgradients, which are challenging the traditional model of platelet function, will also be introduced in the review.