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Although the drugs have available since the 1950s, only recently have pharmacokinetic and pharmacodynamic data been available to guide appropriate use of these drugs. Far more data and global clinical experience exist for colistin, available as the prodrug colistimethate sodium (<jats:styled-content style=\"fixed-case\">CMS<\/jats:styled-content>), compared with polymyxin B. Concerns raised about variability in the ability to achieve therapeutic drug concentrations when dosing <jats:styled-content style=\"fixed-case\">CMS<\/jats:styled-content> have led many clinicians to desire a more pharmacokinetically reliable product. The pharmacokinetic and pharmacodynamic advantages of polymyxin B compared with <jats:styled-content style=\"fixed-case\">CMS<\/jats:styled-content> are compelling, but clinical experience has not consistently corroborated these data. Prospective, comparative data evaluating both drugs in combination with other antimicrobials as well as comparing polymyxin B and <jats:styled-content style=\"fixed-case\">CMS<\/jats:styled-content> directly will inform optimal use of each drug. Some of these investigations are currently under way. 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