The majority of the vertebrate skeleton develops through the process of endochondral ossification and involves successive steps of chondrogenesis, chondrocyte proliferation, and hypertrophic chondrocyte differentiation. Interruption of this program through gene mutations and hormonal or environmental factors contributes to numerous diseases, including growth disorders and chondrodysplasias. While a large number of growth factors and hormones have been implicated in the regulation of chondrocyte biology, relatively little is known about the intracellular signaling pathways involved. Recent data provide novel insights into the mechanisms governing acquisition of new phenotypes within the chondrogenic program and suggest multiple pivotal roles for members of the mitogen-activated protein kinase family and their downstream targets in cartilage development. These data are summarized and discussed here.