The death of a loved one – bereavement – is a universal experience that marks the human mental health condition. Grief – the cognitive, emotional, and behavioral responses to bereavement – is thus experienced by virtually everyone at some point in life, while mourning is a process through which grievers come to terms with the loss envisioning life without the deceased. Although distress subsides over time among most bereaved individuals, a minority will develop a condition recently identified as prolonged grief disorder (PGD). The present review provides a global perspective on bereavement, grief reactions, and PGD. Although the loss of a loved one and grief reactions are in general experienced consistently across different cultures, differences and variations in their expression may exist across cultures. Especially within specific populations that may be more at risk for PGD, possibly due to risk factors associated with the mechanisms of loss (e.g., refugees, migrants, and conflict survivors). The diagnostic criteria for PGD are mostly based on Western grieving populations, and cultural adaptations of PGD treatments are limited. Therefore, cross-cultural development and validation of PGD screening/assessment is critical to support future research on grief reactions and PGD, especially in non-Western contexts, and concerning the potential future global changes and challenges that appear to have a major impact on PGD. More transcultural research on PGD is needed to contextualize and will lead to culture-bound symptom identification of PGD, and the adaptation of current treatment protocols, which may ultimately improve health at the individual level, and health-care systems.