The concept of reversing chronic kidney disease (CKD) has been intensively researched over the past decade. Indeed, as the prevalence of end-stage renal disease is constantly on the rise, the lack of established antifibrotic therapies is a considerable unmet need in clinical practice. Now, the possibility of effective antifibrotic treatment has been established in experimental models of CKD and multiple antifibrotic compounds—in kidney disease, as well as in fibrotic diseases of the skin, liver and lung—are being assessed in clinical trials. These strategies target various components of the fibrotic pathway, from signalling molecules that include transforming growth factor-β, phosphatidylinositide 3-kinase and chemokines to microRNAs. Here, we discuss therapeutic concepts to inhibit or even reverse chronic kidney injury and review the leading candidate antifibrotic drugs to be introduced to clinical use.