Museum specimens play a crucial role in addressing key questions in systematics, evolution, ecology, and conservation. With the advent of high-throughput sequencing technologies, specimens that have long been the foundation of important biological discoveries can inform new perspectives as sources of genomic data. Despite the many possibilities associated with analyzing DNA from historical specimens, several challenges persist. Using avian systems as a model, we review DNA extraction protocols, sequencing technologies, and capture methods that are helping researchers overcome some of these difficulties. We highlight empirical examples in which researchers have used these technologies to address fundamental questions related to avian conservation and evolution. Increasing accessibility to new sequencing technologies will provide researchers with tools to tap into the wealth of information contained within our valuable natural history collections. This article is protected by copyright. All rights reserved.