Altogether, this Research Topic aims to assist both specialists and interested non-specialists and to stimulate further initiatives to unravel the mechanistic involvement of the CXCR4 ligand/receptor family in the detrimental interplay between the comorbidities T2DM, CKD, and CVD, potentially paving the way for new therapeutic initiatives in the future. Here, CXCR4 is linked to type 2 diabetes mellitus.