Chronic kidney disease (CKD) patients require dialysis to manage the progressive complications of uraemia. Yet, many physicians and patients do not recognize that dialysis initiation, although often necessary, subjects patients to substantial risk for cardiovascular (CV) death. While most recognize CV mortality risk approximately doubles with CKD the new data presented here show that this risk spikes to >20 times higher than the US population average at the initiation of chronic renal replacement therapy, and this elevated CV risk continues through the first 4 months of dialysis. Moreover, this peak reflects how dialysis itself changes the pathophysiology of CV disease and transforms its presentation, progression, and prognosis. This article reviews how dialysis initiation modifies the interpretation of circulating biomarkers, alters the accuracy of CV imaging, and worsens prognosis. We advocate a multidisciplinary approach and outline the issues practitioners should consider to optimize CV care for this unique and vulnerable population during a perilous passage.