The heparin family, which includes unfractionated heparin, low-molecular heparin, and fondaparinux, is a class of drugs clinically used as intravenous blood thinners. To date, issues related to both the reversal of anticoagulation and the blood level determination of the anticoagulant at the point-of-care remain: while the only U.S. Food and Drug Administration (FDA) approved antidote for heparin displays serious efficacy and safety drawbacks, the current assays for heparin monitoring are indirect measurements subject to their own limitations and variations. Herein, we provide an update on the numerous recent chemical approaches to tackle these issues, from which it is clear that some new antidotes and sensors for heparin certainly have the potential to exceed current clinical standards. This review aims to review a field that requires close collaborations between physicians, biologists, and chemists in order to foster advances toward clinical translation.