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This paper describes the relationship of Transpersonal Psychology (TP) to the theorizing and treatment of clinical depression. It argues that, rather than TP’s being one of many equivalent clinical lenses that can be applied to depression, TP is actually a necessary framework for understanding the phenomenon of depression, and at least in the case of more severe/chronic depressions, it is required to obtain results beyond mere symptom management. The construct “ungrieved futility” is used to essentialize the structural dynamic nature of depression, and the cybernetic perspective on depression is used to explain why depression’s intrinsic structure mandates a TP lens (what is referred to as depression’s “transphilic” nature). The implications of this view on the treatment of depression are described, in terms of impacts on outcomes and both client and therapist experiences of treatment.