We use baker’s yeast, Saccharomyces cerevisiae, as a model genetic organism in which to study the molecular mechanisms of stress signaling. The biomedical relevance of our work is two-fold. First, we seek to identify novel aspects of signal transduction that are evolutionarily conserved with humans and therefore tell us something about our own biology that may be useful in the treatment of disease. Second, when we identify aspects or components of signaling pathways that are unique to fungi, these often represent potential targets for antifungal drug discovery. Our work centers on the molecular mechanisms involved in the activation and signaling output of two stress-activated MAP kinase (SAPK) pathways — the Cell Wall Integrity (CWI) pathway, which responds to cell wall challenges during growth and morphogenesis, and the High Osmolarity Glycerol (HOG) pathway, which responds to hyper-osmotic stress. We have found in recent studies that, like mammalian SAPK pathways, these two yeast pathways respond to a wide variety of stress conditions in addition to their well-understood functions in the maintenance of the cell wall and osmotic balance. These stresses include DNA damage, metal toxicity, oxidative stress, organic acid stress, and others. We are currently pursuing a very interesting pair of related questions. Specifically, what are the pathways by which such different types of stress stimulate the same SAPKs, and how does their stimulation by these diverse signals result in stress-specific signaling outputs?