The publication of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, (DSM-5) extends a profession and practice-defining direction for family therapy. Warranting and expediting this medicalised direction has been a scientific and administrative coupling of diagnosed symptomatic conditions with evidence-based treatments for addressing those conditions. For systemically or poststructurally oriented family therapists tensions can follow from this direction which we elaborate upon in this article. Specifically, we examine the premises behind this medicalised direction for family therapy, juxtaposing these premises with systemic and post-structural premises of practice. We relate these juxtapositions to tensions family therapists may need to reconcile in their work with families. We close with an overview of this special issue's contributions that pertain to the DSM-5 and family therapy.