Studies over recent years have redeveloped our understanding of uremic cardiomyopathy, defined as left ventricular hypertrophy, congestive heart failure, and associated cardiac hypertrophy plus other abnormalities that result from chronic kidney disease and are often the cause of death in affected patients. Definitions of uremic cardiomyopathy have conflicted and overlapped over the decades, complicating the body of published evidence, and making comparison difficult. New and continuing research into potential risk factors, including uremic toxins, anemia, hypervolemia, oxidative stress, inflammation, and insulin resistance, indicates the increasing interest in illuminating the pathways that lead to UC and thereby identifying potential targets for intervention. Indeed, our developing understanding of the mechanisms of UC has opened new frontiers in research, promising novel approaches to diagnosis, prognosis, treatment, and management. This educational review highlights advances in the field of uremic cardiomyopathy and how they may become applicable in practice by clinicians. Pathways to optimal treatment with current modalities (with hemodialysis and angiotensin-converting enzyme inhibitors) will be described, along with proposed steps to be taken in research to allow evidence-based integration of developing investigational therapies.