Cardiovascular complications are mainly responsible for the high morbidity and mortality in people with diabetes. The awareness of physicians for the importance of primary prevention increased lately and numerous strategies have been developed. The spectrum ranges from pharmacologic treatment to vitamins and dietetic interventions. Some interesting concepts such as focusing on exogenous advanced glycation end products have emerged, but definitive results on their clinical relevance are still lacking. A major problem of the primary prevention is the choice of the method applied for screening, the criteria used to classify risk patients, as well as the choice of therapy. Guidelines provide goals to be achieved and offer alternatives for treatment, but the medical decision has to be made on an individualized basis. In this overview, we will comprehensively focus on the most important pathomechanisms and clinically relevant approaches, aiming at the early diagnosis and treatment of diabetes along with coronary heart disease. When primary prevention fails, we advocate a more aggressive treatment of critically ill patients, followed by optimal secondary prevention meeting on-target goals precisely.