For microorganisms that grow over a wide range of extracellular pH, systems must have evolved to sense and respond appropriately. The human opportunistic pathogen Candida albicans colonizes and infects anatomical sites of diverse pH, including the oral and gastro-intestinal tracts and the vaginal cavity. The ability to sense and respond to neutral-alkaline environments is governed by signal transduction pathways, one of which culminates in the activation of the transcription factor, Rim101p. The RIM101/pacC pathway, which governs pH responses and differentiation, has been the focus of study in both Saccharomyces cerevisiae and Aspergillus nidulans. This pathway has been identified in C. albicans and governs pH responses, dimorphism, and pathogenesis. Although C. albicans and S. cerevisiae are related fungi, it is becoming apparent that there are unique aspects of the pH response and the role the RIM101 pathway plays in this response in C. albicans.