As part of the invited supplement on Death and Dying in the PICU, we reviewed ethical, cultural, and social considerations for the bedside healthcare practitioner prior to engaging with children and families in decisions about limiting therapies, withholding, or withdrawing therapies in a PICU. Clarifying beliefs and values is a necessary prerequisite to approaching these conversations. Striving for medical consensus is important. Discussion, reflection, and ethical analysis may determine a range of views that may reasonably be respected if professional disagreements persist. Parental decisional support is recommended and should incorporate their information needs, perceptions of medical uncertainty, child’s condition, and their role as a parent. Child’s involvement in decision making should be considered, but may not be possible. Culturally attuned care requires early examination of cultural perspectives before misunderstandings or disagreements occur. Societal influences may affect expectations and exploration of such may help frame discussions. Hospital readiness for support of social media campaigns is recommended. Consensus with family on goals of care is ideal as it addresses all parties’ moral stance and diminishes the risk for superseding one group’s value judgments over another. Engaging additional supportive services early can aid with understanding or resolving disagreement. There is wide variation globally in ethical permissibility, cultural, and societal influences that impact the clinician, child, and parents. Thoughtful consideration to these issues when approaching decisions about limitation or withdrawal of life-sustaining therapies will help to reduce emotional, spiritual, and ethical burdens, minimize misunderstanding for all involved, and maximize high-quality care delivery.