Adiponectin secreted from adipose tissue binds to two distinct adiponectin receptors (AdipoR1 and AdipoR2) identified and exerts its anti-diabetic effects in insulin-sensitive organs including liver, skeletal muscle and adipose tissue as well as amelioration of vascular dysfunction in the various vasculatures. A number of experimental and clinical observations have demonstrated that circulating levels of adiponectin are markedly reduced in obesity, type 2 diabetes, hypertension, and coronary artery disease. Therapeutic interventions which can improve the action of adiponectin including elevation of circulating adiponectin concentration or up-regulation and/or activation of its receptors, could provide better understanding of strategies to ameliorate metabolic disorders and vascular disease. The focus of the present review is to summarize accumulating evidence showing the role of interventions such as pharmacological agents, exercise, and calorie restriction in the expression of adiponectin and adiponectin receptors.