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The Diels-Alder reaction and its retro breakdown has garnered increasing research focus due to several of its advantageous properties including, atomic conservation, reversibility, and substituent retention. This is especially true in biomedical application and nanomedicine development which display a preference for rapid, efficient, and clean "click" chemistry reactions allowing for delivery of active ingredients and subsequent release upon temperature elevation. There are multiple variations on the Diels-Alder reaction based around substitution position and materials being coupled which can affect the temperature threshold for and rate of the retro reaction reversal. Hence, the Diels-Alder reaction offers a simple coupling reaction for active ingredients with tailorable release. In this review the incorporation of the Diels-Alder chemistries and linkers within the biomedical and nanomedicine field will be discussed, as well as its use in future potential technologies., (Copyright © 2021 Elsevier B.V. All rights reserved.)