The aim of this narrative review is to analyze the Receptor Activator of NF-κB ligand (RANKL)-Receptor Activator of NF-κB (RANK)-Osteoprotegerin (OPG) pathway in CF, highlighting its role in bone remodeling and its correlation with the inflammatory response, and to evaluate the possible therapeutic implications of targeting drugs at different levels of the pathway based on the available literature. This evidence concerns the gene TNFSF11 and cystic fibrosis.