For over two centuries, the Western Rattlesnake complex has intrigued, inspired, and often infuriated scientists seeking understanding of this polytypic species assemblage across the panoply of biological disciplines. As a consequence, perhaps no species of rattlesnake has received the degree of scientific scrutiny than the Western Group. From the exploration of the American West by 19th Century Natural Historians, to the revolutionary Modern Evolutionary Synthesis of the early 20th Century, to the advent of modern molecular genetics in the late 20th Century, and into the Age of Genomics-Proteomics-Venomics of the 21st Century, the Western Rattlesnake has been a focal point of scientific inquiry. Despite over two centuries of scrutiny, the complex continues to drive novel scientific explorations and discovery.