Antimicrobial resistance, both bacterial and fungal, is a serious threat to global health. The rise in the level of resistant microorganisms has been accompanied by a decline in the level of development of new antibiotics over the past three decades, exacerbating the crisis. Novel chemotypes acting on new targets are particularly desirable. As outlined in this Perspective, organoselenium compounds are an overlooked class of molecules that represent a potential solution to some of these issues. We present here a comprehensive overview of the structures and activities of organoselenium compounds reported to have antimicrobial activity. The diversity of structures and activity profiles supports the hypothesis that further investigation of these compounds is justified, with the Se atom bestowing increased activity on otherwise unremarkable molecules. Concerns over potential Se toxicity appear unwarranted, with organoselenium compounds successfully dosed in humans in gram quantities. With the research community struggling to discover effective antibiotics, organoselenium derivatives warrant a closer look.