The saccharin ring system has gained considerable attention in the past decades, especially in the field of medicinal chemistry. The wide applicability of saccharin derivatives remains the driving force behind the constant development of novel routes and methods that provide new access to the construction of saccharin. Since the functionalization of this heterocycle has proved difficult, except for N- and O-alkylation, novel strategic approaches are much sought-after and thus constitute a great value to any medicinal chemist. In addition to the synthetic novelties introduced into the synthesis and functionalization of this particular heterocycle, the numerous newly discovered biological activities of saccharin and its derivatives are also reviewed. Saccharin may be considered to constitute a privileged framework on account of its role as a key structural element in several biologically active compounds ranging from enzyme inhibitors to receptor ligands and beyond.