The fruit fly, Drosophila melanogaster, is an excellent model system that has a vast set of molecular tools and mutants to dissect the genetic pathways that are responsible for the normal and abnormal cardiac function. While the majority of studies have focused on heart development in the Drosophila embryo, attention has recently focused on the structure and function of the adult fly heart as a model of human heart failure. Here we review strategies to identify novel genes and pathways that cause or modify dilated cardiomyopathy in adult Drosophila.