Assessing drug-induced changes (particularly prolongation) in the QT interval has been the major preoccupation of safety pharmacology since its inception, under the assumption that QT widening represents a surrogate biomarker for torsades de pointes (TdeP) liability. While evidence of changes in QT remains a bane to the development of novel therapeutic agents, non-clinical and clinical methods have been developed (with a certain amount of validation) to limit this potential liability of a new chemical entity (NCE). Because of the associated withdrawal of numerous drugs from clinical use, determining whether or not a drug development candidate exhibits a TdeP liability has been the motivation in the implementation of discussions between 'pharmaceutical companies', academicians, clinicians and regulatory authorities worldwide that has led to the development of the ICHS7A and ICHS7B guidance documents (Anon, 2001, 2005). Simultaneously, it has resulted in the firm establishment of safety pharmacology as a standalone discipline within the drug development scheme (Pugsley et al., 2008). As far as TdeP liability is concerned, QT widening remains the most poignant issue, in that QT widening in humans is immediately regarded as a cause for concern, yet QT widening in preclinical models (and indeed in man) is not a quantitative predictor of TdeP liability (and indeed may not even be a qualitative predictor by itself (Pugsley et al., 2008). The present focused issue of the journal returns to safety pharmacology, and contains papers arising from the 8th annual SPS Meeting that was held in Madison, WI in 2008. Indeed, so many papers have arisen from the meeting that this issue of the Journal is only part 1. Part 2 will be published as the next issue of the Journal. Some topics which have been addressed include whether an assessment method for drugs that produce a shortened QT interval is needed, what the role of the slow component of the delayed rectifier K current (I(Ks)) should be in a safety assessment and whether safety pharmacology endpoints can or should be added to repeat dose Toxicology studies.