Progress towards amelioration and eventual cure of human cognitive disorders requires understanding the molecular signaling mechanisms that normally govern learning and memory. The fly Drosophila melanogaster has been instrumental in the identification of molecules and signaling pathways essential for learning and memory, because genetic screens have produced mutants in these processes and the system facilitates integrated genetic, molecular, histological and behavioral analyses. We discuss the behavioral paradigms available to assess associative learning and memory in the fly, the contributions learning and memory mutants have made to our understanding of the molecular mechanisms that govern learning and memory, and predictions stemming from the nature of the affected genes. Furthermore, we consider the multiple well-established behavioral assays available and the powerful molecular genetics of the fly with regard to development of models of human cognitive disorders and their pharmacological treatment.