Abstract: Chromosomal DNA replication is a fundamental process in the transmission of genetic information through generations. While the molecular mechanism of DNA replication has been studied for a long time, knowledge regarding this process in eukaryotic cells has advanced rapidly in the past 20 years. Yeast genetics contributed profoundly to this rapid advancement. Reverse genetics and genetic screenings identified all genes encoding replication proteins in budding yeast. Moreover, the genetic interactions that were used in screenings and analyses provided an insight into the molecular mechanism of chromosomal DNA replication. Further studies showed that complicated but sophisticated mechanisms govern chromosomal DNA replication. The retrospective view of the genetic approaches used to elucidate DNA replication in eukaryotes, together with current knowledge, tell us the reasons why some of the genetic screenings are successful, and also provide ideas for future directions.