Supercritical fluid (SF) CO2 is receiving a great deal of interest in the scientific and engineering community as a replacement for toxic organic solvents. Analytical chemists employ large quantities of organic solvents during preparation of the sample for analysis. The application of SF extraction with CO2 and modified CO2 to the isolation of active drug components and metabolites from various pharmaceutical and biological matrices is reviewed, Studies are described that deal with spiked drugs in animal feed, residual solvent in drug formulations, and active ingredients in over-the-counter products. The experimental challenges to implementing this technology for trace analysis are discussed. While much of the impetus for working with SFs is prompted by regulatory issues, it would appear that SFs afford the analyst a better-cheaper-faster-safer way of performing drug analysis.