A detailed understanding of the processes governing adipose tissue formation will be instrumental in combating the obesity epidemic. Much progress has been made in the last two decades in defining transcriptional events controlling the differentiation of mesenchymal stem cells into adipocytes. A complex network of transcription factors and cell-cycle regulators, in concert with specific transcriptional coactivators and corepressors, respond to extracellular stimuli to activate or repress adipocyte differentiation. This review summarizes advances in this field, which constitute a framework for potential antiobesity strategies.