The low polarity of the supercritical fluid extraction (SFE) solvent, CO₂, causes problems when applying this technique to polar compounds. The objective of this research was to expand the applicability of SFE to include polar compounds. The first phase of this research investigated "inverse SFE", which is the selective extraction of the matrix while leaving behind the target analytes, as a means of isolating four polar polymyxin sulfate compounds from several challenging matrices due to the liquid-like consistency and the low concentrations (ppm) of the target analytes. Higher recoveries (>100%) were achieved with low RSD's (5.0 and 1.9% for two separate matrices), compared to the conventional method of isolation, solid phase extraction. The second portion of this research investigated the effect of high levels of polar modifier on trapping efficiency. The mode of modifier introduction was found to have a considerable effect on trapping efficiency, as in-line modifier addition rather than matrix spiking was determined to be best when introducing high levels of liquid modifier. Also, three separate mechanisms, aerosol formation, blow-by, and modifier elution, were identified which caused analyte loss at the solid phase trap, and the extraction and trapping conditions for which each mechanism was most favorable were identified. The next phase of this research developed two separate SFE methods which were used to isolate two pharmaceuticals from leaves. Each SFE method reduced the time, sample handling, costs, and liquid solvents needed as compared to the conventional liquid extraction technique. While achieving comparable recoveries, reproducibilities were much improved for the two SFE methods with RSD's of 3.8 and 5.2%, respectively, while the liquid extraction technique yielded RSD's of 14%. The last phase of this research investigated several strategies for improving selectivity in SFE. Three separate strategies for improving selectivity were studied: 1) alternative fluids (pure and modified fluoroform and tetrafluoroethane), 2) pre-extraction, and 3) selective rinsing of the solid phase trap. Advantages were realized with each technique, and it was concluded that they be used in conjunction with one another in order to maximize selectivity. / Ph. D.