There is little information on the evaluation of family functioning in adult patients with chronic non-psychiatric illness. The objective of this systematic review was to identify family functioning assessment instruments of known validity and reliability that have been used in health research on patients with a chronic non-psychiatric illness. We conducted a search in three biomedical databases (PubMed, Science Direct, and Web of Science), for original articles available in English or Spanish published between 2000 and 2019. The review was conducted in accordance with PRISMA guidelines. Fourteen articles were included in the review. The instruments Family Assessment Device, Family Adaptability and Cohesion Evaluation Scales, Family Functioning Health and Social Support, Family APGAR, Assessment of Strategies in Families-Effectiveness, Iceland Expressive Family Functioning, Brief Family Assessment Measure-III, and Family Relationship Index were identified. All of them are reliable instruments to evaluate family functioning in chronic patients and could be very valuable to help nurses identify families in need of a psychosocial intervention. The availability and clinical application of these instruments will allow nurses to generate knowledge on family health and care for non-psychiatric chronic conditions, and will eventually contribute to the health and wellbeing of adults with a non-psychiatric chronic disease and their families.