The lymphatic vasculature is the “sewer system” of our body as it plays an important role in transporting tissue fluids and extravasated plasma proteins back to the blood circulation and absorbs lipids from the intestinal tract. Malfunction of the lymphatic vasculature can result in lymphedema and obesity. The lymphatic system is also important for the immune response and is one of the main routes for the spreading of metastatic tumor cells. The development of the mammalian lymphatic vasculature is a stepwise process that requires the specification of lymphatic endothelial cell (LEC) progenitors in the embryonic veins, and the subsequent budding of those LEC progenitors from the embryonic veins to give rise to the primitive lymph sacs from which the entire lymphatic vasculature will eventually be derived. This process was first proposed by Florence Sabin over a century ago and was recently confirmed by several studies using lineage tracing and gene manipulation. Over the last decade, significant advances have been made in understanding the transcriptional control of lymphatic endothelial cell type differentiation. Here we summarize our current knowledge about the key transcription factors that are necessary to regulate several aspects of lymphatic endothelial specification and differentiation.