In 2008 the United States Food and Drug Administration (FDA) issued a guidance for industry on assessment of cardiovascular risk (CV) in patients treated with new medications for Type 2 Diabetes Mellitus. Numerous cardiovascular clinical outcome trials (CVOTs) have been conducted since then, allowing for better understanding of the pathophysiology and treatment of diabetic macrovascular disease.The results of CVOTs trigger the potential therapeutic differences between the agents from the same class and between classes, and to revise the current guidance to improve efficiency in clinical research. Overall the evidence for an early initiation of cardiovascular treatment interventions in diabetes is strong. Recently the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) have published a new statement for the treatment of hyperglycemia in type 2 Diabetes. The new statement is based on the outcomes of the recent CVOTs and shall be discussed during the presentation. The challenge to treat cardiovascular risk factors and established cardiovascular disease in diabetes is strongly recommended in all new guidelines and has a high input on our daily practice.