Progress in medicine over recent decades has notably increased life expectancy in the Western world. Such advance implies that the treatment of degenerative processes associated with ageing has become one of the major tasks of current medicine and therapeutics. High expectation relies on stem cell research in order to apply cell therapies to ameliorate degenerative processes, remarkably those concerning the circulatory, locomotor and nervous systems. However, the skeletal connective tissues have revealed that cell plasticity is a factor of major importance in regenerative therapies. Most evidence indicates that connective tissue cells of cartilage, tendons, ligaments and fascia share common progenitors during their differentiation, which are regulated by a number of director genes and a panel of miRNAs coupled with transforming growth factor-β signalling. Furthermore, we know that not only stem cells but also differentiated cells from these tissues may dedifferentiate and redifferentiate, even one into another. Hence, modulation of cell plasticity might be a potential target for regenerative therapies in the future. In this review, we highlight classical concepts about the properties and differentiation of the connective tissues and their relation with recent advances in the study of stem cells, significant for regenerative medicine, paying special attention to cartilage and tendons. Copyright © 2011 John Wiley & Sons, Ltd.