Ensuring the continuity of life requires that individual cells and entire organisms can survive not only in ideal environments, but also in conditions of scarcity. When conditions are unfavorable for proliferation, many cells have the capacity to enter a nondividing state, sometimes for years, while retaining their ability to reenter the proliferative cell cycle. 1,2 This state of reversible cell cycle arrest, known as quiescence, is common and can be seen in stem cells, eggs and spores. Some quiescent cells are surprisingly hardy: they can survive long periods of nutrient starvation, cold temperatures and even desiccation. Entry into quiescence is often associated with dramatic changes in metabolism, defined as the uptake of nutrients and the use of these nutrients for the synthesis of macromolecules and energy. Indeed, proliferating and quiescent fibroblasts are expected to have very different metabolic requirements. While proliferating cells must devote much of their metabolic capacity to biosynthesis in order to create the material necessary to form a new cell, quiescent cells are relieved of this steep metabolic requirement. Many but not all quiescent cells respond by downregulating the synthesis of proteins *Correspondence to: Hilary Coller; Email: hcoller@princeton.edu Submitted: 02/22/12; Accepted: 02/27/12 http://dx.doi.org/10. 4161/cc.19879 Quiescence is a state of reversible cell cycle arrest that can grant protection against many environmental insults. in some systems, cellular quiescence is associated with a low metabolic state characterized by a decrease in glucose uptake and glycolysis, reduced translation rates and activation of autophagy as a means to provide nutrients for survival. For cells in multiple different quiescence model systems, including Saccharomyces cerevisiae, mammalian lymphocytes and hematopoietic stem cells, the Pi3Kinase/TOr signaling pathway helps to integrate information about nutrient availability with cell growth rates. Quiescence signals often inactivate the TOr kinase, resulting in reduced cell growth and biosynthesis. However, quiescence is not always associated with reduced metabolism; it is also possible to achieve a state of cellular quiescence in which glucose uptake, glycolysis and flux through central carbon metabolism are not reduced. in this review, we compare and contrast the metabolic changes that occur with quiescence in different model systems. 2 The signals for quiescence vary for different types of cells. Bacteria and yeast can enter stationary phase, a condition in which they cease cell growth and proliferation, in response to depletion of the glucose in their culture medium or in response to deprivation for a specific nutrient. In mammals, the proliferative state of individual cells is regulated by a host of factors that include not only the presence or absence of nutrients, but also cues from proliferative signaling molecules such as mitogens and situational cues. Quiescent T lymphocytes respond to stimulation of their T-cell receptor with the approp...