Osmostress triggers profound adaptive changes in the physiology of the cell with a great impact on gene expression. Saccharomyces cerevisiae has served as an instructive model system to unravel the complexity of the stress response at the transcriptional level. The main signal transduction pathways like the HOG (high osmolarity glycerol) MAP kinase cascade or the protein kinase A pathway regulate multiple specific transcription factors to accomplish large changes in the expression pattern of the genome. Transcription profiling and proteomic studies give us an idea about the impact of osmostress on gene expression and the overall protein composition. Recent genome wide location studies for several transcription factors and signaling kinases involved in the transcriptional stress response shed light on the genomic organization of the osmostress response at the level of the dynamic association of regulators with chromatin. Finally, global surveys of mRNA stability complete our picture of the mechanisms underlying the massive reprogramming of global gene expression, which leads to efficient adaptation to osmotic stress.