In the past, studies using the yeast Saccharomyces cerevisiae enabled major breakthroughs in the understanding of basic cellular and molecular processes. Today, the use of yeast is undergoing a "rebirth" in both fundamental and applied research. Indeed, advances in yeast technology have paved the way for a variety of new genome-wide screening approaches. Experimental strategies using yeast aim to unravel disease-related molecular events and to discover novel medicinal compounds. In this article, the impact of yeast as an experimental tool for disease-related studies is summarized and the use of yeast in high-throughput screenings for pharmacological purposes is evaluated. The recently applied and promising approach of so-called humanized yeast systems is also discussed.