Glycosylation is the process by which glycans (i.e. ‘sugars’) are enzymatically attached to proteins or lipids to form glycoconjugates. Growing evidence points to glycosylation playing a central role in atherosclerosis. Glycosylation occurs in all human cells and post-translationally modifies many signalling molecules that regulate cardiovascular disease, affecting their binding and function. Glycoconjugates are present in abundance on the vascular endothelium and on circulating lipoproteins, both of which have well-established roles in atherosclerotic plaque development. Sialic acid is a major regulator of glycan function and therefore the process of sialylation, in which sialic acid is added to glycans, is likely to be entwined in any regulation of atherosclerosis. Glycans and sialylation regulators have the potential to present as new biomarkers that predict atherosclerotic disease or as targets for pharmacological intervention, as well as providing insights into novel cardiovascular mechanisms. Moreover, the asialoglycoprotein receptor 1 (ASGR1), a glycan receptor, is emerging as an exciting new regulator of lipid metabolism and coronary artery disease. This review summarises the latest advances in the growing body of evidence that supports an important role for glycosylation and sialylation in the regulation of atherosclerosis.