Survival signaling by the erythropoietin (Epo) receptor (EpoR) is essential for erythropoiesis and for its acceleration in hypoxic stress. Several apparently redundant EpoR survival pathways were identified in vitro, raising the possibility of their functional specialization in vivo. Here we used mouse models of acute and chronic stress, including a hypoxic environment and β-thalassemia, to identify two markedly different response dynamics for two erythroblast survival pathways in vivo. Induction of the antiapoptotic protein Bcl-x_L is rapid but transient, while suppression of the proapoptotic protein Bim is slower but persistent. Similar to sensory adaptation, however, the Bcl-x_L pathway “resets,” allowing it to respond afresh to acute stress superimposed on a chronic stress stimulus. Using “knock-in” mouse models expressing mutant EpoRs, we found that adaptation in the Bcl-x_L response occurs because of adaptation of its upstream regulator Stat5, both requiring the EpoR distal cytoplasmic domain. We conclude that survival pathways show previously unsuspected functional specialization for the acute and chronic phases of the stress response. Bcl-x_L induction provides a “stop-gap” in acute stress, until slower but permanent pathways are activated. Furthermore, pathologic elevation of Bcl-x_L may be the result of impaired adaptation, with implications for myeloproliferative disease mechanisms.