Chronic inflammation plays a key role in the development and progression of atherosclerotic cardiovascular disease (ASCVD) and its complications. Despite the use of blood pressure-, lipid-, and glucose-lowering therapies as well as antithrombotic agents, the lifetime residual cardiovascular (CV) risk in patients with ASCVD remains high. Because chronic inflammation remains an unaddressed risk factor, anti-inflammatory therapy has the potential to further lower residual CV risk in these patients. Low-dose colchicine (0.5 mg daily) has emerged as a promising low-cost oral anti-inflammatory therapy for this indication. In patients with chronic coronary syndrome (CCS), low-dose colchicine was well-tolerated and reduced the risk of myocardial infarction, stroke, coronary revascularization, and CV death. However, trials in patients with acute coronary syndrome (ACS) yielded conflicting results, and two trials in patients with ischemic stroke did not show a benefit. In patients with peripheral artery disease (PAD), preliminary observational data suggested a potential benefit, and a randomized trial is currently underway to examine its efficacy in reducing CV and limb events. The long-term safety data for low-dose colchicine in ASCVD are reassuring. Although pooled data from trials in ASCVD show a small (0.55%) absolute increase in the risk of hospitalization for gastrointestinal events, adverse signals were not observed for serious infection, cancer, or severe myotoxicity. In this article, we review the clinical studies of colchicine that examined its risk-benefit for the prevention of CV events in patients with ASCVD, discuss clinical and research implications, and highlight knowledge gaps.