OBJECTIVES: E-prescribing is the electronic transmittal of a prescription to a pharmacy from the point of care.  Electronic health records (EHR) provide greater functionality beyond e-prescribing and improve the availability of pharmacy benefits information and patient medication histories. The objective of this study is to describe the absolute growth in e-prescribing, e-prescribing method changes, growth in pharmacies accepting e-prescriptions, and discuss the impact of federal incentives on the e-prescribing adoption rate. METHODS Pharmacy and prescriber data used for descriptive analyses are from SureScripts (12/2008 - 9/2011).  Standard descriptive statistics and standard regression analyses were used to analyze the data. RESULTS: A total of 95% of all chain, franchise, or independently owned pharmacies in the US route through the SureScripts network. The total number of health care providers prescribing on the SureScripts network has increased significantly over time from approximately 75,000 in December 2008 to approximately 420,000 in January 2012 (p<0.001). The number of e-prescribers has significantly increased in trajectory since 2009, which may be due to the federal incentives for EHRs. Health care providers e-prescribing via EHR systems and via stand-alone e-prescribing systems also increased, although the trajectory of EHR prescribers is much higher. Among current prescribers on the SureScripts network, 80% use an EHR.  Currently, prescription refills/renewals comprise only 16% of total transactions. The percentage of total physicians e-prescribing on the SureScripts network in the US increased during this study period from 2% to 50%. CONCLUSIONS: E-prescribing is the gateway to the improved patient care that health IT promises. Prescription refills/renewals show promising benefits, as they are bi-directional health information exchange.  Despite this, physicians have faced many barriers to implementation, with cost and workflow change as the primary challenges. Government incentive programs appear to have increased e-prescribing use among health care providers.