The beneficial role of the trace element selenium (Se) in human health has been known for several decades and is attributed both to low-molecular-weight Se compounds and to its presence within 25 selenoproteins in the form of the amino acid selenocysteine (Sec). Incorporation of Sec into selenoproteins involves decoding of the UGA codon. This process requires multiple features, such as the Sec-insertion sequence (SECIS) element and protein factors, including a specific elongation factor EFSec and the SECIS-binding protein 2, SBP2. Although many selenoproteins remain functionally uncharacterized, some of their known functions include redox regulation of intracellular signaling, redox homeostasis, and thyroid hormone metabolism. Pathologically, reduced expression of selenoproteins has been directly linked with the congenital muscle disease referred to as selenoprotein N (SEPN)-related myopathy and with thyroid-hormone metabolism defects (deficiency of deiodinases due to genetic defects in SBP2). From a broader, less well defined aspect, selenium compounds and selenoproteins have been linked to prevention of some forms of cancer, Alzheimer's disease, cardiovascular disease, and life span. This forum summarizes recent advances in our understanding of important roles of selenium, selenoproteins, and factors involved in selenoprotein synthesis in health and disease and discusses potential targets for therapy.