Nanobiology is a fast-emerging discipline that brings the tools of nanotechnology to the biological sciences. The introduction of new techniques may accelerate the development of highly specific biomedical treatments, increase their efficiency, and minimize their side effects. Introducing foreign bodies into the complex machinery of the human body is, however, a great and humbling challenge, as past experience has shown. In order for nanobiology to reach its full potential, we must devise a means to alter the properties of nanoparticles, as expressed in the human body, in a predictable manner. Computer-aided methods are the natural option to speed up the development of these technologies. Yet, the procedures for annotation and simulation of nanoparticle properties must be developed and their limitations understood before computational methods can be fully exploited. In this review we will compare the state of development of nanoscale simulations in the biological sciences to that of the computer-aided drug design efforts in the past, tracing a historical parallel between both disciplines. From this comparison, lessons can be learned and bottlenecks identified, helping to speed up the development of computer-aided nanobiodevice design tools.