One of the most useful metaphors for driving scientific and engineering progress has been that of the “machine.” Much controversy exists about the applicability of this concept in the life sciences. Advances in molecular biology have revealed numerous design principles that can be harnessed to understand cells from an engineering perspective, and build novel devices to rationally exploit the laws of chemistry, physics, and computation. At the same time, organicists point to the many unique features of life, especially at larger scales of organization, which have resisted decomposition analysis and artificial implementation. Here, we argue that much of this debate has focused on inessential aspects of machines – classical properties which have been surpassed by advances in modern Machine Behavior and no longer apply. This emerging multidisciplinary field, at the interface of artificial life, machine learning, and synthetic bioengineering, is highlighting the inadequacy of existing definitions. Key terms such as machine, robot, program, software, evolved, designed, etc., need to be revised in light of technological and theoretical advances that have moved past the dated philosophical conceptions that have limited our understanding of both evolved and designed systems. Moving beyond contingent aspects of historical and current machines will enable conceptual tools that embrace inevitable advances in synthetic and hybrid bioengineering and computer science, toward a framework that identifies essential distinctions between fundamental concepts of devices and living agents. Progress in both theory and practical applications requires the establishment of a novel conception of “machines as they could be,” based on the profound lessons of biology at all scales. We sketch a perspective that acknowledges the remarkable, unique aspects of life to help re-define key terms, and identify deep, essential features of concepts for a future in which sharp boundaries between evolved and designed systems will not exist.