A systemic disease is one that affects a number of organs and tissues, or the body as a whole. Systemic diseases include endocrine, metabolic, nutritional, multisystem (rheumatic) and HIV disease. Cardiovascular involvement is a common and underestimated problem in systemic diseases, and may present with disease associated cardiac involvement at diagnosis or later in the course of the systemic disease. The cardiac involvement in these diseases is usually silent or oligo-symptomatic and includes different pathophysiological mechanisms such as, myocardial inflammation, infarction, diffuse, subendocardial vasculitis, valvular disease and different patterns of fibrosis. Furthermore, acuity of heart involvement may be underestimated due to non-specific cardiac signs, and finally, most of patients are female and unable to exercise, due to arthritis or muscular discomfort/weakness or may have limited acoustic window, due to increased breast size. Cardiovascular magnetic resonance (CMR), due to its ability to reliably assess cardiac anatomy, function, inflammation, stress perfusion-fibrosis, aortic distensibility, and iron and fat deposition, constitutes an excellent tool for early diagnosis of heart involvement, risk stratification, treatment evaluation and long-term follow-up of patients with cardiac disease due to systemic diseases.