Self-immolative polymers (SIPs) have been under development for over a decade, and efforts for their application followed shortly after their inception. One main area of application of SIPs is biomedicine, where they are used to construct devices and biosensors, develop new biotechnology abilities, or directly interface with the living system. Where traditional polymers are stable at room temperature, SIPs undergo rapid degradation when a labile capping group is removed, allowing SIPs to offer a highly unusual degradation profile compared with traditional polymers. This review summarizes the recent efforts to leverage the unique properties of SIPs for biomedical purposes, which are categorized into sensors, drug delivery, and biotechnology. By doing so, this review aims to stimulate future studies in this rapidly growing and promising area.