Increases in hydrogen peroxide can initiate protective responses to limit or repair oxidative damage. However, hydrogen peroxide signals also fine-tune responses to growth factors and cytokines to control cell division, differentiation, and migration. Here we discuss some of the mechanisms by which hydrogen peroxide is sensed and utilized as a signaling molecule to regulate diverse biological processes. We also discuss how the localization and levels of hydrogen peroxide, antioxidants, and the cellular metal composition together influence the nature of the response.