Sponsors considering the use of electronic patient-reported outcome (ePRO) for their clinical trials can choose from a wide variety of diverse solutions. These choices include the very paper-like digital pen; telephone based systems such as IVRS; web based solutions; the well established flavors of device-based solutions (for both home and site use) and more recently, SMS based solutions using the subjects own mobile phone. When faced with this number of options, study teams may be tempted to fall back to the default and familiar choice of paper. Paper diaries have been used for thirty-plus years of clinical research, but they are not always the best choice. There are well-documented problems with the compliance and accuracy of at-home paper diaries. Today's ePRO options and technologies can successfully overcome these problems. Perhaps more significantly, clinical trial study teams are learning that issues with paper based data collection are minor in comparison with the task of establishing the validation status of the patient reported outcome (PRO) instrument selected. Whether a paper-based or electronic method is used to collect PRO data intended to support labeling claims, regulators are likely to review the psychometric properties of the data collection instrument. Some instruments meet the current requirements of validity, reliability and sensitivity to change, but there are a large number of instruments created during the 1990's that require further development and validation to meet the high standards demanded for regulatory approval in the U.S. for use as part of a claim.