Background: The use of oligonucleotides as therapeutic agents has elicited a great deal of interest. Basic understanding and evaluation of the pharmacokinetic properties of oligonucleotides is foundational to their appropriate design and application. Objective: To review the primary pharmacokinetic properties that drive successful use and delivery of oligonucleotides. Methods: The primary data set available in the published literature for summarizing the pharmacokinetic properties of oligonucleotides exists for single strand phosphorothioate antisense oligonucleotides and their chimeric chemical modifications (second generation). Where possible, data from other classes of compounds are contrasted with this base class. Results/conclusion: Although there are several different classes of oligonucleotides being developed as therapeutic agents, their pharmacokinetic properties by class are primarily a function of their backbone chemistry and the resulting chemical relationship to biological stability and plasma protein binding properties.