Inactivated poliovirus vaccine (IPV) is not only increasingly used on a global basis but also is a component of many combination vaccines. Standardization and control of IPV continues to be a challenge for manufacturers and regulators. A rat immunogenicity assay is currently recommended by many authorities, including WHO, as the definitive in vivo potency. Alternative in vitro assays to determine D-antigen content have been developed and are routinely used in some countries to assess IPV potency assay. However, the other less reliable in vivo immunogenicity assays are also used (e.g. monkey, chick). We review some of the regulatory challenges facing current and future IPV assessment, with a focus on the relevance of in vivo and in vitro tests, considerations for Sabin derived IPV and discussion of future efforts for standardization.