Diabetes mellitus (DM) is a very common disease which, if a good glycemic control is not achieved, can lead to serious chronic complications such as cardiovascular disease, retinopathy, nephropathy and neuropathy. Selfmonitoring of blood glucose is a fundamental tool for the proper adjustment of the treatment of diabetes and, at present, it is based mainly on capillary blood obtained by finger-prick (the classical glucometers). Since this method is painful and the strips are expensive, investigators have been attracted by the idea of using a non-invasive device for determining blood glucose which would permit more frequent testing and a tighter control of diabetes. The non-invasive measurement of blood glucose is based on the ability of the glucose molecule to interact with various chemical or physical methods. Nevetheless, in spite of some encouraging results and the efforts made over the past 30-40 years, there is no device available at present for use in clinical practice. A possible explanation might be the combination between the specific features of each method and the specific characteristics of diabetic patients, which make them respond differently to physical and chemical methods when compared to their healthy counterparts. In this paper we will give an overview of the noninvasive devices tested so far and their implications for the clinical management of the diabetic patient.