Pancreatic beta-cell mass, under normal circumstances, is maintained at an optimal level to provide for a normal metabolic load. It should not be viewed as static, and slow in turning over. Indeed, the adult beta-cells adults are plastic and able to increase their population to adapt to changes in metabolic demand, such as in pregnancy or nondiabetic obesity. Net changes in beta-cell mass are reflective of the amount of growth (i.e., the sum of betacell replication, neogenesis and size) minus the degree of beta-cell death (i.e., the sum of beta-cell apoptosis, necrosis and autophagic cell death). In some circumstances, such as prolonged obesity and insulin resistance, the beta-cell works under pressure trying to meet the metabolic demand, but eventually succumbs to a collective number of stresses that lead to an increase in beta-cell death, a subsequent reduction in beta-cell mass, and the eventual onset of type 2 diabetes. In this chapter, what is currently known about mechanisms of beta-cell growth and death are looked at in detail, with an emphasis on adaptive mechanisms in obesity and pregnancy and the signal transduction pathways involved in the control of beta-cell growth. Also, the various stresses on the beta cell that may lead to the onset of type 2 diabetes will be outlined and the inflammatory signaling pathways that contribute to increased beta-cell apoptosis/necrosis examined.