This chapter provides an overview of the main stress responses modulated by neuropeptides of the crustacean hyperglycemic hormone (CHH) family. The current scenario of upstream regulation of CHHs is presented here. Numerous sequence variants, splicing-isoforms, and posttranslational modifications of CHHs point to a wide functional diversification of these peptides. Other than the classical main CHH-mediated cascade resulting in energy mobilization, new aspects focused on CHH chirality are demanding deeper efforts on the characterization of their target and mode of action. Moreover, new CHH variants with immune-related functions have been recently described, broadening further the role of such a neuropeptides family.