To improve or sustain patients’ quality of life (QoL) is the main goal of palliative care. In palliative care as in healthcare in general, QoL is commonly conceptualized as health-related quality of life (HRQoL) which is the self-perceived health status of an individual and encompasses measurable components that are related to health, disease, illness, and medical interventions. Patient-reported outcome (PRO) measures is the term presently used for any measure that collects responses directly from the patients and includes measures on QoL, HRQoL, functions, and symptoms. In spite of substantial evidence on the positive outcomes of using PRO instruments (questionnaires) in the clinic, such use still faces barriers from the health system and the healthcare providers. The content and the measurement capabilities of present PRO instruments can also be a barrier. The selection of PRO instruments is recommended to follow a sequential approach. Define overall aim(s), define the research question(s), agree upon the key outcome(s), and select the appropriate set of questions/questionnaires guided by the primary and secondary outcomes. In general, it is recommended to use a generic or a disease-specific questionnaire and supplement with domain-specific questionnaire(s) for measurement of fatigue, pain, anxiety, depression, or other symptoms/functions reflecting the purpose(s) of the data collection.