The goal of personalized medicine is to treat each patient with the best drug: optimal therapeutic benefit with minimal side effects. The genomic revolution is rapidly identifying the genetic contribution to the diseased state as well as its contribution to drug efficacy and toxicity. The ability to perform genome-wide studies has led to an overwhelming number of candidate genes and/or their associated variants; however, understanding which are of therapeutic importance is becoming the greatest unmet need in the personalized medicine field. A related issue is the need to improve our methods of identifying and characterizing therapeutic drugs in the context of the complex genomic landscape of the intact body. Drosophila have proven to be a powerful tool for understanding the basic biological mechanisms of human development. This article will review Drosophila as a whole animal tool for gene and drug discovery. We will examine how Drosophila can be used to both sort through the myriad of hits coming from human genome-wide scans and to dramatically improve the early steps in pharmaceutical drug development.