Believe it or not, skin complications are sometimes the first sign that you may have diabetes. Recent studies have already shown a relationship between skin autofluorescence and diabetes complications, as well as the predictive value of skin autofluorescence for total and cardiovascular mortality in type 2 diabetes. Skin from diabetic and nondiabetic mice and humans underwent biomechanical testing. The aim of this review was to systematically review all articles on the association between skin autofluorescence (SAF), measured by the AGE Reader, and complications of diabetes. Some of these conditions are painful, while others are found to be embarrassing. Single end points were the development of diabetes-associated retinopathy, neuropathy, and (micro)albuminuria. At baseline, both murine and human diabetic skin was biomechanically inferior compared to nondiabetic skin, with decreased maximum stress and decreased modulus (P < 0.001 and < 0.05, respectively). This systematic review of literature showed an association of SAF with end-organ complications in diabetes, except retinopathy, in all seven studies. Wash minor cuts with soap and water. More prospective studies, with a longer period of follow-up, larger group size, and strict definitions of complications and end points, are needed to demonstrate the potential role and benefit in clinical management before the widespread use of the AGE Reader can be recommended.