Art and science work is experiencing a dramatic rise coincident with burgeoning Science and Technology Studies interest in this area. Science has played the role of muse for the arts, inspiring imaginative reconfigurations of scientific themes and exploring their cultural resonance. Conversely, the arts are often deployed in the service of science communication, illustration, and popularization. STS scholars have sought to resist the instrumentalization of the arts by the sciences, emphasizing studies of theories and practices across disciplines and the distinctive and complementary contributions of each. The manifestation of this commonality of creative and epistemic practices is the emergence of ASTS as the interdisciplinary exploration of art-science. This handbook defines the modes, practices, crucial literature, and research interests of this emerging field of Art and Science Studies. It explores the questions, methodologies, and theoretical implications of scholarship and practice that arise at the intersection of art and science studies with the goal of demonstrating how the arts are intervening in STS. Drawing on methods and concepts derived from STS and allied fields including visual studies, performance studies, design studies, science communication, as well as aesthetics and the knowledge of practicing artists and curators, ASTS is predicated on the capacity to see both art and science as constructions of human knowledge-making. Accordingly, it posits a new analytical vernacular in enabling new ways of seeing, understanding, and thinking critically about the world. This handbook provides scholars and practitioners already familiar with the themes and tensions of art-science with a means of connecting across disciplines. It also proposes organizing principles for thinking about art-science across the sciences, social sciences, humanities, and arts. Encounters with art and science become meaningful in relation to perceptual habits, background knowledge, and cultural norms. As the chapters in this handbook demonstrate, a variety of STS tools can be brought to bear on art-science so that systematic research can be conducted on this unique set of knowledge-making practices.