Senescence is a highly regulated process, eventually leading to cell and tissue disintegration: a physiological process associated with nutrient (e.g. nitrogen) redistribution from leaves to reproductive organs. Senescence is not observed in young leaves, indicating that repressors efficiently act to suppress cell degradation during early leaf development and/or that senescence activators are switched on when a leaf ages. Thus, massive regulatory network re-wiring likely constitutes an important component of the pre-senescence process. Transcription factors (TFs) have been shown to be central elements of such regulatory networks. Here, we used quantitative real-time polymerase chain reaction (qRT-PCR) analysis to study the expression of 1880 TF genes during pre-senescence and early-senescence stages of leaf development, using Arabidopsis thaliana as a model. We show that the expression of 185 TF genes changes when leaves develop from half to fully expanded leaves and finally enter partial senescence. Our analysis identified 41 TF genes that were gradually up-regulated as leaves progressed through these developmental stages. We also identified 144 TF genes that were down-regulated during senescence. A considerable number of the senescence-regulated TF genes were found to respond to abiotic stress, and salt stress appeared to be the major factor controlling their expression. Our data indicate a peculiar fine-tuning of developmental shifts during late-leaf development that is controlled by TFs.