Kidney fibrosis is a hallmark of chronic kidney disease (CKD) and a potential therapeutic target. However, there are conceptual and practical challenges to directly targeting kidney fibrosis. Whether fibrosis is mainly a cause or a consequence of CKD progression has been disputed. It is unclear whether specifically targeting fibrosis is feasible in clinical practice because most drugs that decrease fibrosis in preclinical models target additional and often multiple pathogenic pathways (eg, renin-angiotensin-aldosterone system blockade).