The present invention provides variants of C-type natriuretic peptide (CNP) comprising one or more deletions; additions of and/or substitutions with natural amino acids, unnatural amino acids and/or peptidomimetics (including peptide bond isosteres); amino acid extensions; and/or other chemical moieties such as, e.g., poly(ethylene glycol) and hydrophobic acids. The CNP variants are useful as therapeutic agents for the treatment of diseases responsive to CNP, including but not limited to bone-related disorders such as, e.g., skeletal dysplasias and achondroplasia, and vascular smooth muscle disorders such as, e.g., restenosis and arteriosclerosis.