Cell response to stress at the transcriptional level is characterized by the rapid expression of a large set of genes. In yeast Saccharomyces cerevisiae this gene activation is determined by the action of two types of activators--HSF and partially redundant Msn2 and Msn4. While HSF activation mechanisms are relatively well established during the last decade, the mechanisms of regulation by Msn2/4 started to clarify only recently. Some of the important aspects of Msn2/4 regulation include nuclear-cytoplasmic shuttling and targeted degradation of these factors at gene promoters during transcription activation. These and other mechanisms will be discussed in the current review.