Background: Over the past two decades, various research teams have designed and applied instruments to measure the quality of life of families with a member who has a disability. A recent systematic review on the state of the Family Quality of Life in early care identified that many of these studies collected data only from the mothers. The present study aimed to investigate whether there is a bias in participant selection in these types of studies. Method: A systematic review of the scientific literature was conducted in three databases—Scopus, Web of Science, Eric—from 2000 to 2022. A total of 72 empirical studies were identified. Results: The findings indicate that most studies examining the Family Quality of Life were based on the information of a single informant per family unit. The profiles of participants according to the research objective are quite similar. In one-third of studies, the authors reported that family members who participate cannot be represented by only mothers or one participant per household. Conclusions: Given the dynamic and collective nature of the construct, the application of a systemic approach is necessary.