Background: Religion and spirituality (R/S) impact how African Americans (AAs) cope with serious illness, yet are infrequently addressed in patient-clinician communication. Objectives: To explore AAs with advanced heart failure and their family caregivers' (FCGs) preferences about R/S in patient-clinician communication. Methods: An embedded qualitative interview within a parent randomized trial about the role of R/S in the illness experience and in clinician interactions with patients and FCGs in a Southern U.S. state. Transcribed interviews were analyzed using constant comparative analysis to identify emergent themes. Results: AA participants (n = 15) were a mean age of 62 years, were female (40%), and had >high school diploma/GED (87%). AA FCGs (n = 14) were a mean age of 58; were female (93%); had >high school diploma/General Education Development (GED) (93%); and were unemployed (86%). Most (63%) were patients' spouses/partners. All patients and FCGs were Protestant. Participants reported the critical role of R/S in living with illness; however, patients' and FCGs' perspectives related to inclusion of R/S in health care communications differed. Patients' perspectives were as follows: (1) R/S is not discussed in clinical encounters and (2) R/S should be discussed only if patient initiated. FCGs' perspectives about ideal inclusion of R/S represented three main diverging themes: (1) clinicians' R/S communication is not a priority, (2) clinicians should openly acknowledge patients' R/S beliefs, and (3) clinicians should engage in R/S conversations with patients. Conclusion: Key thematic differences about the role of R/S in illness and preferences for incorporating R/S in health care communications reveal important considerations about the need to assess and individualize this aspect of palliative care research and practice.