Abstract Selenium (Se) is an essential trace element, and dietary Se sources can be metabolized to a shared metabolite, hydrogen selenide (H 2 Se). H 2 Se is the key precursor for the biosynthesis of Se‐containing biomolecules and may be considered as an emerging gasotransmitter. Development of chemical tools and materials for controllable release of H 2 Se is significant in understanding Se‐related chemical biology and may open new avenues for treating some diseases. In this review, we focus on the development of H 2 Se donors and precursors as well as their biological applications. In addition, we discuss the reaction mechanisms of these donors, the design strategies for fluorogenic donors, and future prospects of the H 2 Se field. We anticipate that this review would promote the development of advanced H 2 Se donors as potentially pharmacological research tools and help to further unearth the H 2 Se chemical biology.