<p>Atherosclerosis is a disease of large and medium arteries that can lead to life-threatening cardiovascular and cerebrovascular consequences, such as myocardial infarction and stroke. Moreover, atherosclerosis is a major contributor to cardiovascular-related mortality in individuals with diabetes mellitus. Diabetes aggravates the pathobiological mechanisms that underlie the development of atherosclerosis. Currently available anti-atherosclerotic drugs or strategies solely focus on optimal control of systemic risk factors, including hyperglycaemia and dyslipidaemia, but do not adequately target the diabetes-exacerbated mechanisms of atherosclerotic cardiovascular disease, highlighting the need for targeted, mechanism-based therapies. This Review focuses on emerging pathological mechanisms and related novel therapeutic targets in atherosclerotic cardiovascular disease in patients with diabetes.</p>