Proteases are important regulators of cell behavior, survival, and apoptosis. They communicate to cells directly through a special class of G-protein-coupled receptors known as protease-activated receptors (PARs). N-terminal PAR proteolysis unmasks a neo-N-terminus, which serves as a tethered ligand to activate PARs. Using this unique irreversible activation mechanism, PARs relay information across cell membranes. The year 2020 is the 30th year since discovery of the first member of this family, PAR1. In this illustrated review, we highlight achievements in the PAR field over the past 3 decades. Additionally, the known expression profiles of PARs in human tissues and across species are portrayed. We also illustrate the tethered ligand activation mechanism, which is unique to PARs, and PAR regulatory mechanisms. PAR1 was originally named "thrombin receptor" because thrombin was the first protease identified to activate PAR1. However, over the past 30 years, a growing number of proteases have been found to cleave PARs and trigger differential downstream signaling depending on cleavage site, cell type, and species. We exemplify the diversity of PAR1-mediated signaling outcomes in platelets and endothelial cells as pertinent examples to the hemostasis, thrombosis, and vascular biology fields. Further, the termination and regulation of PAR signaling via endocytosis and currently available pharmacologic approaches are depicted. We conclude with portrayal of clinically translational aspects of PAR biology including pharmacologic manipulation and single-nucleotide polymorphisms.