Changes in MEKC chemical selectivity that are induced by changes in the headgroup structure of cationic surfactants are examined. Separations of acidic, basic, and hydrophobic solutes are examined. The acidic analytes are comprised of methoxyphenols, which are of interest due to their prevalence in wood smoke. The basic solutes consist of compounds often found in forensic urine analysis, and represent typical basic pharmaceuticals. The hydrophobic solutes are six pharmaceutical corticosteroids used in replacement therapy of adrenocortical insufficiency and nonspecific treatment of inflammatory and allergic conditions. The role of the headgroup was found to be quite significant when analyzing acidic compounds with not all the surfactants being able to resolve all of the analytes. The headgroup, also induced migration order switches among the acidic analytes. All of the surfactants examined here in were found to be suitable for the analysis of basic analytes with each surfactant providing unique selectivity. The hydrophobic solutes were separated best with the larger more hydrophobic surfactant headgroups. The steroid separation with these two surfactants was achieved without the use of organic modifiers or a mixed micellar phase.