Since 1994, YC-1 (Lificiguat, 3-(5′-hydroxymethyl-2′-furyl)-1-benzylindazole) has been synthesized, and many targets for special bioactivities have been explored, such as stimulation of platelet-soluble guanylate cyclase, indirect elevation of platelet cGMP levels, and inhibition of hypoxia-inducible factor-1 (HIF-1) and NF-κB. Recently, Riociguat®, the first soluble guanylate cyclase (sGC) stimulator drug used to treat pulmonary hypertension and pulmonary arterial hypertension, was derived from the YC-1 structure. In this review, we aim to highlight the synthesis and structure–activity relationships in the development of YC-1 analogs and their possible indications.