Interpersonal neurobiology (IPNB) is a burgeoning interdisciplinary field that focuses on ways in which relationships shape and transform the architecture and functioning of the human brain. IPNB points to four specific conditions that appear to encourage the emergence of empathy. Further, these conditions, when gathered together, may constitute the core components of a spirituality of compassion. Following definitions and a discussion of interdisciplinary method, this essay delineates IPNB's main tenets and demonstrates ways in which IPNB sheds light on important aspects of human empathy and compassion. Drawing on this analysis, it introduces the four conditions that encourage the emergence of empathy in individuals and groups and shows why they may be central elements of a spirituality of compassion. A case study, in which the Native American Ojibwe practice of the talking circle is described and assessed through the lens of the IPNB-derived spirituality of compassion, demonstrates the evaluative usefulness of this set of conditions.