Our current clinical doctrine and practice is based upon a classification of diabetes which relies mainly on some clinical manifestations/criteria, rather than markers of the pathophysiological mechanisms of the disease. An improved classification based on such biological markers (i.e. of insulin resistance, beta cell dysfunction, autoimmunity) may assist in clinical decision and may offer the opportunity of an optimized therapeutic strategy. We address here some important questions that have not yet been clarified, e.g. which markers/indicators best define the main pathogenic mechanisms of the disease in a patient with diabetes and what threshold values are relevant for this purpose.