Families often experience an irresolvable type of loss called “ambiguous loss.” Through no fault of their own, their grief process is frozen and remains unresolved, sometimes for a lifetime. This unique kind of loss was first described by Boss through research with families of persons missing physically or psychologically, and subsequently introduced to family therapists (Boss, 1999, 2006; Boss & Greenberg, 1984) and the general public (Boss, 2011). Here we review the concepts of ambiguous loss for family therapists, identify its effects on family systems, and present guidelines for therapy and intervention for more global application. Finally, we focus on the person of the therapist, because in order to help families with ambiguous loss, we as therapists must first increase our own tolerance for ambiguity.