Platelets have intricate signaling mechanisms and participate in a breadth of cellular interactions. This diversity is frequently unrecognized. In addition to being the chief cellular effectors of haemostasis, platelets are innate inflammatory cells that have previously unrecognized molecular pathways and synthetic capacities, which can link innate and adaptive responses in the immune continuum. Characterization of these features and parallel in vivo observations identify new sentinel, surveillance and information-transfer functions. Recent observations indicate that platelets have key roles in adaptive responses to microbial and antigen challenge, in addition to their well known acute defensive activities in tissue injury, and suggest that these mechanisms can be dysregulated in disease. Ongoing characterization of the platelet transcriptome, secretome and proteome also suggest that additional functions of platelets relevant to innate and adaptive immunity remain to be discovered. This Review is the third in a series on interactions between haemostasis and inflammation.