Platelets have a flagship role in the maintenance of haemostasis, which demands that they can respond to their local environment rapidly and in a controlled manner. To perform this life-critical task, platelets bear several receptors that are able to engage with proteins found in the subendothelial tissue environment and in plasma. These receptors receive environmental cues from the vasculature and transmit these signs as molecular signals across the platelet membrane. This induces a host of molecular, morphological and metabolic changes to the platelet, triggering it to alter its shape, behaviour and activation status. These processes that turn a quiescent detached platelet into an activated proadhesive entity occur within seconds and involve specific molecular pathways and processes. This chapter will discuss the major molecular players that trigger and control the mechanisms by which platelets become adhesive, with a focus on platelet receptor signalling events and newly described contributions of mechanosensitive receptors.