Cellular communication network factor 2 (CCN2, formerly known as ‘connective tissue growth factor’ or ‘CTGF’) was the subject of anti-fibrotic drug development programs, largely in FibroGen, starting in the mid-1990s. This led to the development of FG-3019 (pamrevlumab) as a lead drug that was used initially to target diabetic nephropathy and subsequently pancreatic cancer, pulmonary fibrosis and Duchenne’s muscular dystrophy. All these programs failed clinically; diabetes in early development, and the others at Phase III. Could these failures have been anticipated? Is ‘CTGF’ dead as an anti-fibrotic target? What might have been done differently or could be done differently in the future? This personal commentary—based on years of experience first at FibroGen working on the ‘CTGF’ program and then as an independent academic researcher---aims to address at least some of these issues.