Supercritical fluids are an attractive medium for the formation of microparticulate solid phases having physical characteristics that are difficult to obtain by alternative routes. Typical operating conditions are mild, and the products are dry and pure, eliminating the need for downstream processing. The physical routes to particle formation from supercritical fluids fall into two broad categories: rapid expansion of supercritical solutions (RESS), and the supercritical anti-solvent process (SAS). The former route is used when the solid product is appreciably soluble in the supercritical fluid; the latter, when the solubility is low. These techniques allow the processing of a very wide spectrum of materials. The basic principles of  RESS and SAS will be explained and examples will be presented, including the formation of ceramic precursor powders, polymeric fibers, and bioerodible polymer microspheres. The formation of protein powders suitable for controlled release or aerosolized delivery to the lungs is a promising application of supercritical fluids, and will be discussed in detail. A variety of proteins can be processed into 1-5 micron particles that can be stored at ambient temperature for over one year and recover their biological activity upon redissolution in an aqueous medium. Supercritical fluids can also be used to fractionate protein mixtures into solid precipitates whose composition can be sensitively controlled through manipulation of the pressure.