Process synthesis is a body of knowledge as essential to chemical engineering as fluid mechanics, heat & mass transfer, reaction engineering, and the other foundation subjects of our profession. Process synthesis of separation systems has matured to the point that if sufficient physical and chemical property data are available, vast numbers of process alternatives can be systematically evaluated to find the best process configuration for the task. We will discuss the present state of the art and how we arrived there during the last century. The new century, however, calls for something different that builds from our current knowledge but focuses on the very early stages of process development where business ventures have not yet been selected from among the long list of possible investment opportunities. At this early stage there is limited knowledge of all aspects of the business case. To make good early decisions, synthesis methods are needed based on preliminary experimental data, property estimation, qualitative and semi-quantitative data, heuristics, and numeric calculations, to rapidly generate manufacturing schematics and to estimate the chances for both technical and business success. The desired methodology will not only suggest a good processing route, but should also provide guidance to project managers for planning subsequent experiments to be performed by the chemists and engineers leading the early development work.