Usability is a critical factor in the acceptance, safe use, and success of health IT. The User-Centred Design process is widely promoted to improve usability. However, this traditional case by case approach that is rooted in the sound understanding of users' needs is not sufficient to improve technologies' usability and prevent usability-induced use-errors that may harm patients. It should be enriched with empirical evidence. This evidence is on design elements (what are the most valuable design principles, and the worst usability mistakes), and on the usability evaluation methods (which combination of methods is most suitable in which context). To achieve this evidence, several steps must be fulfilled and challenges must be overcome. Some attempts to search evidence for designing elements of health IT and for usability evaluation methods exist and are summarized. A concrete instance of evidence-based usability design principles for medication-related alerting systems is briefly described.