Abstract: Over the past several years, the C-type natriuretic peptide (CNP) has emerged as an important regulator of cartilage homeostasis and endochondral bone growth. In mice, genetic ablation of CNP or its cognate receptor NPRB results in marked dwarfism. Conversely, overexpression of CNP rescued the phenotype of CNP- deficient mice. In vitro studies demonstrated the exogenous CNP infuenced chondrocyte differentiation, and proliferation and matrix synthesis at a concentration dependent manner. Evidence indicates that enhanced CNP signaling may prevent growth retardation and protect cartilage in patients with infammatory joint disease. This review focuses on the role of CNP signaling in bone and cartilage tissue and its potential therapeutic applications.