One intriguing challenge in modern biology is to understand how cells respond to, and distinguish between different stressing stimuli. Evidence accumulated in recent years indicates that a network of signaling pathways extends from the plasma membrane to the very core of the cell nucleus to transduce environmental changes into a graded transcriptional response. Although many steps still remain unclear, studies on the stress-activated protein kinase (SAPK) pathways and related mechanisms provide insight into the biochemistry that regulates signal transmission and leads to outcomes such as cell adaptation and differentiation. This review focuses on selected topics of current interest related to the sensing of stress signals in cells of the fission yeast Schizosaccharomyces pombe. Because signaling pathways appear to be evolutionarily well conserved, yeasts may be useful models to learn how higher eukaryotes sense and respond to stresses at the cellular level.