Despite evident roles for immunity orchestrated by Th1 cells and Th17 cells in host defense, the role for Th2 cells remains enigmatic, as helminths are highly adapted and poorly controlled by type 2 immunity in humans and animals. The discovery of innate lymphoid cells, ILC2s, that programmatically express type 2 cytokines, enables a fresh look at the evolutionary role of this response without regard for antigen specificity. ILC2s develop during fetal life, position in peripheral organs, and express IL-5 following birth. ILC2s express tissue-specific transcriptomes, which identify key signals that control their activation in distinct tissues. For example, small intestine ILC2s constitutively express the receptor for IL-25, even in germfree mice, thus identifying a key role for this cytokine in regulating ILC2 activity in this tissue. As such, ILC2s reveal a tissue-specific geography that begins to uncover their key role in organ-specific homeostasis through response to local signals that enable dynamic responses to sustain tissue and systemic health.