High-throughput screenings based on the use of chemical genetic approaches to Saccharomyces cerevisiae do allow for the selection of chemical compounds able to modulate a phenotype selected from the yeast model. The synthesis of large chemical libraries led to the ideation of a new approach (chemical genetics) free of the limitations associated with classical genetics. The simple yeast model S. cerevisiae represents a good choice for the selection of molecules when screening complex compound libraries and for dissection of the way of action of a selected molecule, thus acting as a beacon along the dark path of drug discovery. The availability of the complete yeast genome sequence allowed for the construction of mutants knocked out for every gene. The continuously increasing number, precision and reliability of novel techniques and the parallel growth of exploitable chemical compound libraries grants the possibility to explore previously unpredictable universes with pharmaceutical and medical interests.