Very important R&D efforts are presently dedicated to applications of supercritical fluids (SCFs) in the pharmaceutical industry, especially for formulation and particle design, but few companies have acquired some know-how in process scale-up, in compliance with the constraints imposed in this industry traceability, Good Manufacture Practises (GMP), and sterility. In this paper based on our experience gathered when developing several formulation processes and building tens of SCF plants during the past decade, we will present the different processes now available for drug formulation, the guidelines to operate the optimal choice, and the general scale-up rules with the specific constraints related to pharmaceutical plants, illustrated by experimental results.