What does it mean to be human? This question has made a meteoric career for itself, becoming a focal point of almost every thread of the transhumanist debate. Significant as it is, the question eludes any definitive answer, since it directly engenders an array of related queries. This Special Issue questions our notions of the human being, human subjectivity, superiority and uniqueness, which tend to be underpinned by simplistic and simplifying dichotomies entrenched in western philosophy, science and art. By articulating the problems we face in understanding and defining the human and the nonhuman, this Special Issue offers an insight into the current transhumanist discourse. Crossing the boundaries of disciplines and definitions, the contributors propose an assemblage of methodological and conceptual scaffoldings to build on in this project.