In an organism, different organ systems are highly specialised for performing dedicated functions. However, it is increasingly becoming clear that the organ systems do not function in isolation but are rather extensively dependent on each other. This phenomenon is known as inter-organ communication and is a novel paradigm of exocrine signaling. In this minireview, we discuss the theoretical implications of this kind of crosstalk and the resources available for practical demonstration of the same. We focus on the fruit fly, Drosophila melanogaster, and the zebrafish, Danio rerio. Both the model organisms are amenable to genetic manipulation and have been largely used to address many pending questions in all the fields of biology using cutting-edge cellular, molecular, and imaging techniques and tools. Both the organisms also offer the advantages of having organ systems functionally equivalent to those of humans to dissect how the development and functions of organs are established in dialogue with others.