Drosophila melanogaster is one of the most widely used genetic model systems in biology. The ease of working in an invertebrate model system allows the design and execution of many experiments that would be infeasible in a vertebrate model. Although the strength of the fly as a model system lies primarily in the ease of genetic manipulation, it is flexible enough that biochemical and proteomic approaches can also be used to build a more comprehensive study. Here we present a pair of complementary protocols that we have used to examine sirtuin biology in Drosophila. First, we describe our protocol for measuring lifespan in flies expressing a gene of interest under the inducible control of the Gene-Switch system. Finally, we describe a method for performing chromatin immunoprecipitation on adult flies, including some of the difficulties associated with using this technique in chitinous tissue.