Results from in vitro toxicity tests have been reported for several decades. Methods for several in vitro toxicity tests have been formalised, accompanied by both national and international guidelines for toxicity test batteries. Cigarette smoke (cigarette smoke condensate/total particulate matter, “whole smoke”) has been shown to elicit positive responses in many of these assays. The CORESTA In vitro Toxicity Testing of Tobacco Smoke Task Force was established in 2002, “to prepare a report covering the rationale and strategy for conducting in vitro toxicity testing of tobacco smoke” and “to identify key procedures based upon internationally recognised guidelines, adapted to accommodate the nature and unique properties of tobacco smoke”. The Task Force’s mandate subsequently modified as follows: “To conduct a proficiency testing programme to evaluate cigarette smoke using a common experimental protocol and the Task Force’s recommended test battery”. While Task Force proficiency trials have primarily focused on “cigarette smoke condensate” (smoke particulate extracted in DMSO), in vitro evaluation of “whole smoke” has become an increasingly active discussion topic. This presentation will provide a brief review of in vitro toxicity testing, a summary of Task Force accomplishments and some thoughts on in vitro toxicity testing in a regulatory context.