All microorganisms must adapt to the pH of their environment. One aspect of this adaptation, particularly important for organisms that grow over a wide pH range, is the ability to express appropriately genes whose roles ultimately involve functions at the cell surface or in the environment. Genes encoding permeases, secreted enzymes, enzymes involved in synthesis of exported metabolites such as toxins and antibiotics, and probably enzymes modifying secreted proteins posttranslationally all fall into this category. Here we discuss the most recent findings on the transcriptional regulatory system in fungi that enables such genes to be expressed only when the ambient pH is conducive to their ultimate functions. The intriguing issue of how pH is sensed and how the resulting signal is transmitted to the transcription factor involves at least one late endosome component. Proper functioning of the regulatory system responding to ambient pH is essential for fungal pathogenicity of both animals and plants.