Health benefits of moderate wine consumption have been studied during the past decades, first in observational studies and more recently, in experimental settings and randomized controlled studies. Suggested biological pathways include antioxidant, lipid regulating, and anti-inflammatory effects. Both the alcoholic and polyphenolic components of wine are believed to contribute to these beneficial effects. Although several of these studies demonstrated protective associations between moderate drinking and cardiovascular disease, atherosclerosis, hypertension, certain types of cancer, type 2 diabetes, neurological disorders, and the metabolic syndrome, no conclusive recommendations exist regarding moderate wine consumption. Yet, it is suggested that the physician and patient should discuss alcohol use. In the CASCADE (CArdiovaSCulAr Diabetes & Ethanol) trial, 224 abstainers with type 2 diabetes were randomized to consume red wine, white wine or mineral water for two years. Here, we summarize our previous findings, offer new evidence concerning the differential effects of wine consumption among men and women, and further suggest that initiating moderate alcohol consumption among well-controlled persons with type 2 diabetes is apparently safe, in regard to changes in heart rate variability and carotid plaque formation.