Chondrogenesis is a key process in skeletogenesis since endochondral ossification requires the formation of a cartilaginous template. Knowledge of molecular mechanisms regulating chondrogenesis is extremely valuable not only to understand many human disorders but also in regenerative medicine. Embryonic skeletogenesis is an excellent model to study this mechanism. Most cartilages share the cellular basis underlying chondrogenesis but the high heterogeneity in morphologies of the different skeletal elements appears to be generated by differential participation of a variety of chondrogenic signals. Here we overview the regulatory factors responsible for chondrogenesis concluding that early chondrogenic signals for the digit cartilages differ from those implicated in the formation of other axial and appendicular skeletal components. BioEssays 29:725–737, 2007. © 2007 Wiley Periodicals, Inc.