Platelets are small anucleate cellular fragments that are released by megakaryocytes and safeguard vascular integrity through a process termed ‘haemostasis’. However, platelets have important roles beyond haemostasis as they contribute to the initiation and coordination of intravascular immune responses. They continuously monitor blood vessel integrity and tightly coordinate vascular trafficking and functions of multiple cell types. In this way platelets act as ‘patrolling officers of the vascular highway’ that help to establish effective immune responses to infections and cancer. Here we discuss the distinct biological features of platelets that allow them to shape immune responses to pathogens and tumour cells, highlighting the parallels between these responses.