Chronic thymus involution associated with aging results in less efficient T cell development and decreased emigration of naïve T cells to the periphery. Thymic decline in the aged is linked to increased morbidity and mortality in a wide-range of clinical settings. Negative consequences of these effects on global health make it of paramount importance to understand the mechanisms driving thymic involution and homeostatic processes across the lifespan. There is growing evidence that thymus tissue is plastic and that the involution process might be therapeutically halted or reversed. The thymus is also acutely sensitive to stress resulting in involution and decreased T cell production. Acute involution is a complication of many stress settings, including infection, malnutrition, starvation, and irradiation or immunosuppressive therapies. Systemic rises in glucocorticoids and inflammatory cytokines are known to contribute to thyme atrophy; however, little is know about intrathymic mechanisms that may actively contribute to thymus atrophy or initiate thymic recovery following stress events.