OBJECTIVES: To enable researchers to better understand the regulatory requirements for inclusion of patient-reported outcome (PRO) measures as efficacy endpoints for the development and approval of drugs for generic pain and analgesic indications, plus three pain-related diseases (i.e., migraines, rheumatoid arthritis [RA], and systemic lupus erythematosus [SLE]).  This research reviews, contrasts, and compares the European Medicines Agency (EMA) and US Food and Drug Administration (FDA) medical guidelines in these conditions. METHODS: A targeted search was conducted for recent (2010-2015) European and US medical guidelines in the conditions mentioned.  Information pertaining to PROs within these guidelines was extracted and compared.  Attention was paid to similarities, differences, and gaps across these guidelines. RESULTS: Both EMA and FDA consistently recommend the use or development of reliable and valid measures across all disease areas and emphasized the importance of measuring symptoms from the patient perspective.  For example, both authorities recommend the assessment of intensity for pain and analgesic indications; assessment of migraine-associated symptoms (nausea, vomiting, photophobia, phonophobia) for migraine treatment efficacy; and measurement of fatigue and other relevant symptoms for patients with SLE.  For RA, the EMA recommends assessment of pain intensity through the use of a PRO measure.  More often, EMA guidelines emphasize the requirement of assessing health-related quality of life (HRQoL) or functioning through PRO measures.  This is not to say that HRQoL is not addressed by FDA guidelines (e.g., measurement of physical and emotional function and HRQoL in pain, assessment of physical function in RA); however, examples of specific assessments are more prominent within EMA guidelines.  In contrast, FDA guidelines are more specific regarding how best to evaluate disease symptoms. CONCLUSIONS: While similarities between EMA and FDA medical guidelines exist, variations between guidelines highlight the need for sponsors to become familiar with and incorporate these guidelines early on in the drug development process.