Massachusetts payers and providers have encouraged clinician usage of e-Prescribing technology to improve patient safety, enhance office practice efficiencies, and reduce medical costs. This report describes three early pilot e-Prescribing projects as case studies. These projects identified the e-Prescribing needs of clinicians, illustrated key issues that made implementation difficult, and clarified the impact of various types of functionality. The authors identified ten key barriers: (1) previous negative technology experiences, (2) initial and long-term cost, (3) lost productivity, (4) competing priorities, (5) change management issues, (6) interoperability limitations, (7) information technology (IT) requirements, (8) standards limitations, (9) waiting for an "all-in-one solution," and (10) confusion about competing product offerings including hospital/Integrated Delivery System (IDN)-sponsored projects. In Massachusetts, regional projects have helped to address these barriers, and e-Prescribing activities are accelerating rapidly within the state.