Symptoms are important patient-reported outcomes (PRO), which help to evaluate the impact of diseases and treatments and assess quality of care. Thorough symptom assessment is a challenge, as patients in palliative settings are often polysymptomatic and easily fatigued. There is no consensus about standardization of symptom assessment in palliative medicine. The available research provides some methodological guidance, but the psychometric properties of structured multisymptom assessments are largely understudied. New approaches may improve the efficacy of clinical assessment and create instruments with greater clinical utility. In this article, we discuss current methodological concepts of symptom assessment in clinical practice, specifically with reference to symptom questionnaires appropriate for palliative medicine.