Purpose of Review Selenium, a trace element, is ubiquitous in the environment. The main source of human exposure is diet. Despite its nutritional benefits, it is one of the most toxic naturally occurring elements. Selenium deficiency and overexposure have been associated with adverse health effects. Its level of toxicity may depend on its chemical form, as inorganic and organic species have distinct biological properties. Recent Findings Nonexperimental and experimental studies have generated insufficient evidence for a role of selenium deficiency in human disease, with the exception of Keshan disease, a cardiomyopathy. Conversely, recent randomized trials have indicated that selenium overexposure is positively associated with type 2 diabetes and high-grade prostate cancer. In addition, a natural experiment has suggested an association between overexposure to inorganic hexavalent selenium and two neurodegenerative diseases, amyotrophic lateral sclerosis and Parkinson’s disease. Summary Risk assessments should be revised to incorporate the results of studies demonstrating toxic effects of selenium. Additional observational studies and secondary analyses of completed randomized trials are needed to address the uncertainties regarding the health risks of selenium exposure.