The article reviews the interplay between platelets and hyperlipidaemia in the development of atherosclerosis. Platelets, which are involved in thrombosis and inflammation, can be activated by native low-density lipoprotein (nLDL) and oxidized LDL (oxLDL), leading to increased platelet reactivity and pro-atherosclerotic effects. nLDL binds to the platelet-specific LDL receptor ApoE-R2', while oxLDL binds to scavenger receptors such as CD36, lectin-type oxidized LDL receptor 1 (LOX-1), and scavenger receptor class A 1 (SR-A1). Platelet activation by nLDL and oxLDL induces various intracellular signaling pathways, including the activation of focal adhesion kinase, p38 MAPK, and protein kinase C, which contribute to platelet aggregation, secretion, and adhesion. Platelets also influence lipid metabolism by enhancing LDL oxidation and promoting foam cell formation through the release of platelet-derived factors such as platelet factor 4 (PF4) and transforming growth factor β (TGFβ). PF4 inhibits LDL binding and uptake, while TGFβ modulates LDL metabolism in different cell types. The article discusses the therapeutic potential of targeting the platelet-hyperlipidaemia interplay, including the use of hypolipidemic and antiplatelet drugs, and highlights the need for further research to understand the complex mechanisms involved in this interplay.The article reviews the interplay between platelets and hyperlipidaemia in the development of atherosclerosis. Platelets, which are involved in thrombosis and inflammation, can be activated by native low-density lipoprotein (nLDL) and oxidized LDL (oxLDL), leading to increased platelet reactivity and pro-atherosclerotic effects. nLDL binds to the platelet-specific LDL receptor ApoE-R2', while oxLDL binds to scavenger receptors such as CD36, lectin-type oxidized LDL receptor 1 (LOX-1), and scavenger receptor class A 1 (SR-A1). Platelet activation by nLDL and oxLDL induces various intracellular signaling pathways, including the activation of focal adhesion kinase, p38 MAPK, and protein kinase C, which contribute to platelet aggregation, secretion, and adhesion. Platelets also influence lipid metabolism by enhancing LDL oxidation and promoting foam cell formation through the release of platelet-derived factors such as platelet factor 4 (PF4) and transforming growth factor β (TGFβ). PF4 inhibits LDL binding and uptake, while TGFβ modulates LDL metabolism in different cell types. The article discusses the therapeutic potential of targeting the platelet-hyperlipidaemia interplay, including the use of hypolipidemic and antiplatelet drugs, and highlights the need for further research to understand the complex mechanisms involved in this interplay.