Platelets express several immunoreceptor tyrosine-based inhibitory motif (ITIM)-containing receptors, which regulate platelet production, platelet activation, adhesion and thrombus stability, and influence both haemostatic and immune responses. In this chapter, we detail the structure, expression, ligands and signalling pathways of this family of receptors, and cover their biological relevance in platelets and megakaryocytes. PECAM-1, G6b-B and LAIR-1 (megakaryocyte-specific) modulate platelet activation. CEACAM-1/2 and LILRB2 balance platelet adhesion and immune interactions. TLT-1 enhances platelet aggregation post-activation, in addition to playing a role in cancer progression. The downstream signalling proteins, SHP-1 and SHP-2, are essential for the inhibitory signalling of these receptors, and their loss can lead to platelet hyperactivation, increasing thrombotic risk. In this chapter, we also discuss strategies for therapeutic targeting and fine-tuning of platelet reactivity. Collectively, this family of receptors play distinct roles in platelet function and regulation, presenting novel opportunities for treatments.