<b><i>Introduction:</i></b> Overweight and obesity lead to numerous complications and their treatment. The associated costs represent a health and sociopolitical burden. Therefore, the development of overweight and obesity is of great importance for health policy. <b><i>Methods:</i></b> The Gutenberg Health Study (GHS), a population-based observational study of individuals aged 35–74 years in the city of Mainz and the district of Mainz-Bingen, examined current data on the prevalence and development of overweight and obesity and their association with concomitant diseases and medication use. <b><i>Results:</i></b> Among men, 48.1% were overweight and 26.3% had obesity. Among women, these proportions were 32.1% and 24.1%, respectively. Elevated body mass index (BMI) was associated with numerous complications, particularly insulin resistance and type 2 diabetes, arterial hypertension, elevated triglycerides and low HDL cholesterol, and cardiovascular disease. Accordingly, medications to treat these conditions were used significantly more often in individuals with elevated BMI. During the 10-year observation period, mean weight increased in the population. Both men and women had a moderate but significant increase in BMI compared to men and women of the same age at baseline. Individual weight changes over the 10-year observation period, on the other hand, were age-dependent. In the two younger age decades, weight gain was observed, while in the oldest age decade, mean body weight decreased. <b><i>Conclusion:</i></b> These current data confirm that overweight and obesity are associated with relevant complications and that these complications lead to significant use of appropriate medications. The study also suggests that there is a significant trend toward increased prevalence of obesity (BMI ≥30) over the 10-year period.