The WHO ranks smoking and alcohol consumption as the first and third leading causes of the global burden of disease in industrialized countries, using disability-adjusted life years (DALYs) as a combined measure of premature death and disability. Smoking is responsible for 12.2% of all DALYs and alcohol consumption for 9.2%. For example in Germany, annually 110,000–140,000 humans die prematurely because of cigarette smoking and 40,000 because of alcohol drinking. In Europe and the USA, more than 20% of all hospitalized men and more than 9% of all hospitalized women suffer from alcohol-associated diseases. In Germany, about 2.0 million people in the age group 18–64 years (3.8% of all Germans) are alcohol abusers and 1.3 million people (2.4%) are alcohol-dependent. Alcohol can cause acute as well as chronic damage in nearly all body organs. Smoking damages also nearly every human body organ and is worldwide the most important single preventable health risk factor as well as the main cause for premature mortality in industrial countries. One third of the adult Germans as well as of the world population are active smokers; men smoke more frequently than women (34.0 vs. 25.1%). In this review a short overview will be given on the most important deleterious effects of alcohol and smoking. The most recent data about the pathophysiological relevance of non-alcoholic compounds of alcoholic beverages will also be discussed.