Glucose monitoring devices represent an exciting frontier in diabetes research. Great efforts have been dedicated to the development of non-invasive glucose monitoring devices, which may considerably improve the quality of life for people suffering from diabetes and facilitate their compliance for glucose monitoring. This manuscript reviews past, current and emerging non-invasive glucose monitoring techniques and devices and presents the major challenges they face. Poor glucose specificity and sensitivity, physiological time lag, calibration process and human factors perspective are discussed. Since incorporating user requirements into device development may potentially increase user acceptance and improve patient safety and device effectiveness, special attention is given to usability, user experience and applicability for home use, thus extending previous published reviews.