Many cardiovascular drugs in the pipeline will fail to demonstrate a clear clinical benefit when evaluated in large-scale clinical outcome trials; which are costly, require lengthy follow-up, and can potentially expose patients to unforeseen risks. There exists an enormous gap between early mechanistic studies demonstrating proof-of-principle drug efficacy in preclinical models, and successful translation of these therapies into everyday clinical practice. To help overcome this challenge, cardiovascular imaging techniques can be applied to quantify early changes in disease severity owing to drug intervention, or lack thereof, with the aim of informing subsequent clinical outcome trials. This approach can be used to direct valuable resources towards development of drugs most likely to provide real clinical impact. The rationale here is that “surrogate” imaging outcomes can be powered using far less subjects than clinical outcomes in drug trials, as each participant will contribute an imaging endpoint regardless of whether they then go on to develop a clinical event. In addition, drug efficacy can be more rapidly tested using imaging markers as there is no need to wait long periods of time for clinical outcomes to occur. Imaging endpoints in clinical trials might also be used in the future to identify specific sub-groups of patients who are more likely than others to respond to targeted pharmacotherapies in cardiovascular disease—so-called “precision medicine.” This article will discuss the potential scope of imaging to improve drug efficacy testing of current and emerging disease-modifying therapies in atherosclerosis.