In the last century, genetics has developed into one of the most powerful tools for addressing basic questions concerning inheritance, development, individual and social operations and death. Here we summarize the current approaches to these questions in four of the most advanced models organisms: Saccharomyces cerevisiae (yeast), Caenorhabditis elegans (worm), Drosophila melanogaster (fly) and Mus musculus (mouse). The genomes of each of these four models have been sequenced, and all have well developed methods of efficient genetic manipulations.