Analytical chemists today are confronted with a variety of very sensitive and powerful techniques which take them to more and more sensitive levels of analysis. Along with the sensitivity come the interferences. Fortunately, today's analyst is also armed with a plethora of clean up techniques to aid in the removal of the interferences. SPE is one of the most powerful of those techniques. It allows for sensitivity and selectivity, which most techniques will not provide together. As powerful as this technique is, it falls victim to the old adage, �A little knowledge can be a dangerous thing.� This presentation is aimed at providing a background on the several mechanisms that are at work in SPE and how the analyst can fine tune these mechanisms to get the maximum performance out of the technique. An emphasis will be placed on ion exchange and how to make it work for you. All mechanisms will be accompanied by examples and data supporting the findings. No matter what the technique�LC/MS, GC/MC, ion chromatography, electrophoresis, LC, GC�proper use of SPE will provide the analyst with cleaner extracts and better signal to noise ratios which will in the long run provide better results and less downtime on equipment.