The genomes of all organisms examined contain transposons whose uncontrolled movement threatens genome function. Fortunately, host cells have evolved defense mechanisms to minimize the level of transposition. In this review we discuss recent work showing that proteins involved in signal transduction and RNA transcription/DNA repair inhibit Ty1 retrotransposition in the yeast Saccharomyces cerevisiae. On the basis of these examples, we hypothesize that the level of Ty1 retrotransposition may be modulated in response to environmental stress signals that affect cellular differentiation and DNA repair.