Diabetes mellitus is an increasingly common chronic disease that has a great impact not only in terms of clinical effects, but also in terms of economic burden worldwide. Expenditures due to diabetes derive essentially from direct and indirect costs. Current estimates of global healthcare expenditures due to diabetes are US$376 billion and are expected to increase to US$490 billion by 2030. In particular, costs associated with diabetes-related complications represent the most relevant part of the national healthcare expenditure for diabetes and are higher than the costs of managing diabetes itself. The major expenditure depends on the type and the number of complications: cardiovascular complications increase direct costs, especially for hospitalization. Moreover, diabetic comorbidity has a greater economic impact on the health expenditure in comparison with those patients without diabetes. In Europe, the CODE-2 study was the first attempt to evaluate the costs of diabetes: the annual costs per patient were estimated at €2384 and the highest value, €2991, was registered in Italy. This indicates an overall annual cost of €5170 million for the whole Italian population with diabetes. Current estimates for 2010 healthcare expenditure for diabetes are US$105 billion (10% of total healthcare expenditure, US$2046 per person) for the whole European region, and US$11 billion (9% of total healthcare expenditure, US$2087 per person) for Italy. More studies are needed in order to better define the real significance of the healthcare costs of diabetes in Italy. An effective therapy with a good metabolic control can reduce the risk of complications and represents a valid strategy from an economic point of view.