Clinical decision support (CDS) rules that are written generically for use in any health care setting require customization when implemented by a particular practice or health care system (HCS). This process has been found typically to require considerable time and effort, as well as IT expertise and is an obstacle to wider sharing and use of best practice clinical knowledge. This is particularly true for smaller non-academic practices or HCSs. For example, each HCS must indicate when a rule should trigger, the method by which health professionals are alerted when it triggers, with whom a rule should interact when data are needed, any modifications of thresholds, timing for alerting, and nature and form of transmission of advice or actions as a result of the rule firing. We call such considerations setting-specific factors (SSFs), and consider the customization of a rule using SSFs as stage 3 in a 4-stage rule refinement model, which was originally developed as part of the Morningside Initiative [1].