Click chemistry has had a significant impact in the field of materials science over the last 10 years, as it has enabled the design of new hybrid building blocks, leading to multifunctional and responsive materials. One key application for such materials is in the biomedical field, such as gene or drug delivery. However, to meet the functional requirements of such applications, tailored degradability of these materials under biological conditions is critical. There has been an increasing interest in combining click chemistry techniques with a range of degradable or responsive building blocks as well as investigating new or milder chemistries to design click delivery systems that are capable of physiologically relevant degradation. This Feature Article will cover some of the different approaches to synthesize degradable click delivery systems and their investigation for therapeutic release.