Crassulacean acid metabolism — or CAM photosynthesis — was described in the early to mid 20th century, and our understanding of the metabolic pathway was later expanded upon through detailed biochemical analyses of carbon balance. Soon after, scientists began to study the ecophysiological implications of CAM, and a large part of this early work was conducted in the genus Agave, in the subfamily Agavoideae of the family Asparagaceae. Today, the Agavoideae continues to be important for the study of CAM photosynthesis, from ecophysiology of CAM species, to the evolution of the CAM phenotype, and the genomics underlying CAM traits. Here we review past and current work on CAM in the Agavoideae, highlighting especially the work of Park Nobel in Agave, and focusing on the powerful comparative system the Agavoideae has become for studying the origins of CAM. We also highlight new genomics research and the potential for studying intraspecific variation within species of the Agavoideae, particularly species in the genus Yucca. The Agavoideae have served as an important model clade for CAM research for decades, and undoubtedly will continue to help push our understanding of CAM biology and evolution in the future.