Present treatment strategies of type 2 diabetes are unsatisfactory. At diagnosis, most oral antidiabetic agents are effective on blood glucose control, but with time metabolic control deteriorates whatever therapeutic modality is used. The reasons for treatment failure are the natural history of the disease and the necessary implication of the patient in the management of blood glucose control on a constant basis. News treatments thus have to be developed acting on either insulin resistance or insulin secretion or both. We discuss here present and future developments which aim to decrease insulin resistance. In the last 10 years, multiple therapeutic targets have been identified in appetite control, such as the endocannabinoid system and glucagon-like-peptide 1, in insulin signalling and in the control of cellular energy balance such as AMP kinase. These developments should allow a better management of type 2 diabetes and its complications.