Nanoscience now enables creation of ultrasmall electronic devices that offer unprecedented opportunities for sensing. Transitioning these devices from the realm of one-of-a-kind “feats” into robust, reproducible nanosystems useful for medical and biological research is a monumental challenge. Only the very first steps have been taken towards this end, even though such efforts are absolutely crucial for realizing the promise of "active" nanotechnology. At least two essential elements must be in place to realize the vast applications potential that awaits. First, an unfamiliar fusion of technologies is required, one that melds techniques from surface biochemistry and microfluidics with sensor technologies from nanoelectronics, nanomechanics, and nanophotonics. Second, robust methods for large-scale nanobiotechnological integration are required, and these must engender identifiable routes to production en masse. This disciplined assemblage of disparate technologies is crucial, whether for fundmental discovery work in medicine and the life sciences, or for the development of future clinical products. The requisite methodology is probably more familiar to the commercial sector than to academia. Despite impressive recent achievements in what I term "unit" nanoscience (which focuses upon individual phenomena and novel structures), nature's systems-nanotechnology still far outstrips what is engineerable today. For example, the mammalian acquired immune response represents a profoundly adaptive system that provides essentially single-molecule sensitivity to pathogens. In this light, harnessing cellular systems within hybrid devices appears to have immense potential for early disease detection, drug discovery, and fundamental medical and biological research. Today’s micro- and nanoscale technologies can provide the requisite tools for such applications. We are managing some awkward first steps toward these ends, embedding nanoscale biosensor arrays into microfluidic systems to form chip-based electronic "laboratories" for cell biology. When fully realized, this approach will permit simultaneous observation and control of multiple intra- and inter-cellular interactions. This, in turn, will reverse-engineering of biochemical networks through the techniques of systems biology, but at the level of the individual cell. There is an inevitability about such pursuits; they are increasingly being carried out by laboratories worldwide. Ultimately, active nanobiotechnology will enable a detailed real-time window into the complexity of cellular processes.