Plants exhibit both mitotic and postmitotic senescence. Mitotic senescence, also known as proliferative senescence, occurs when germline-like meristem cells lose their ability to undergo mitotic cell division. Unlike replicative senescence in yeast and human cells in culture, mitotic senescence in plants is not controlled by telomere shortening. Postmitotic senescence, an active degenerative process, occurs in organs such as leaves and floral petals. Substantial progress has been made toward understanding the molecular mechanisms of postmitotic senescence (especially leaf senescence). Leaf senescence is a form of programmed cell death that can be regulated by an array of endogenous factors and environmental cues. Gene expression is required in order for leaf cells to die. In Arabidopsis thaliana, up to 2500 genes (including more than 130 that encode transcription factors) are transcribed during leaf senescence. Mutant analysis and functional genomics approaches have revealed important roles for several of these genes in leaf senescence. In addition to summarizing our current understanding of senescence in plants at the molecular level, this Review compares mechanisms of senescence in yeast and animal systems.