Selenium levels in soil generally reflect its presence in food and the Se levels in human populations. Se food content is influenced by geographical location, seasonal changes, protein content and food processing. Periodic monitoring of Se levels in soil and food is necessary. Diet is the major Se source and approximately 80% of dietary Se is absorbed depending on the type of food consumed. Se bioavailability varies according to the Se source and nutritional status of the subject, being significantly higher for organic forms of Se. Se supplements can be beneficial for subjects living in regions with very low environmental levels of Se. Several strategies have been followed: (1) employment of Se-enriched fertilizers; (2) supplementation of farm animals with Se; (3) consumption of multimicronutrient supplements with Se. Nevertheless, detailed investigations of possible interactions between Se supplements and other food components and their influence on Se bioavailability are needed. Suppliers also need to provide more information on the specific type of Se used in supplements. In addition, research is lacking on the mechanisms through which Se is involved in hepatocyte damage during hepatopathies. Although Se potential as an antioxidant for the prevention of cardiovascular diseases (CVD) is promising, additional long-term intervention trials are necessary. As a result, indiscriminate Se supplements cannot be reliably recommended for the prevention of CVD in human beings. Some interesting findings reported an association of Se intake with a reduced prevalence and risk for prostate and colon cancer. However, random trials for other cancer types are inconclusive. As a final conclusion, the general population should be warned against the employment of Se supplements for prevention of hepatopathies, cardiovascular or cancer diseases, because benefits of Se supplementation are still uncertain, and their indiscriminate use could generate an increased risk of Se toxicity.