How is the genome of a single cell able to program the development of complex organisms such as ourselves? Model systems such as the nematode worm, fruit fly, zebrafish, laboratory mouse and pluripotent stem cells have provided most of the answers. Classic forward and reverse genetic approaches used to unveil these processes are discussed. Validated molecular mechanisms governing key spatial and temporal events are explained. Knowledge gained from these experimental models has informed much of our understanding of the genetics of human development and disease.