Regulation of developmental processes as well as host defense and repair mechanisms requires the maintenance of a delicate balance of positive and negative regulatory signals. TGF-beta, a molecule known for its many diverse activities, can promote or inhibit cell growth and function. Disruption of the balance between these opposing activities can contribute to aberrant development, malignancy, or pathogenic immune and inflammatory responses. TGF-beta transgenic mouse studies highlight the essential function(s) of TGF-beta and its receptors and provide insight to potential therapeutic approaches to manipulate TGF-beta expression.