Chronic kidney disease (CKD) is affecting more and more individuals over time. The importance of the increased prevalence is enhanced by the close association with the increased risk of poor individual outcomes such as death, fatal and non-fatal cardiovascular (CV) events and progression to end stage kidney disease (ESKD). ESKD requires replacement treatment such as hemodialysis (HD), a particular and complex context that unfortunately has been rarely considered in observational studies in the last few decades. The current perspective of HD as a bridge to kidney transplant requires greater attention from observational and experimental research both in the prevention and treatment of CV events in ESKD patients. We present a narrative review by performing a literature review to extrapolate the most significant articles exploring the CV risk, in particular coronary artery disease (CAD), in ESKD and evaluating possible innovative diagnostic and therapeutic tools in these patients. The risk of CAD increases linearly when the estimated glomerular filtration rate (eGFR) declines and reached the most significant level in ESKD patients. Several diagnostic techniques have been evaluated to predict CAD in ESKD such as laboratory tests (Troponin-T, N-terminal pro b-type natriuretic peptide, alkaline phosphatase), echocardiography and imaging techniques for vascular calcifications evaluation. Similarly, treatment is based on lifestyle changes, medical therapy and invasive techniques such as coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI). Unfortunately in the literature there are no clear indications of the usefulness and validity of biomarkers and possible treatments in ESKD patients. Considering the ESKD weight in terms of prevalence and costs it is necessary to implement clinical research in order to develop prognostic reliable biomarkers for CV and CAD risk prediction, in patients with ESKD. It should be highlighted that HD is a peculiar setting that offers the opportunity to implement research and facilitates patient monitoring by favoring the design of clinical trials.