Introduction: Although the negotiation of new meaning is a common goal in almost all family therapy, and various approaches offer theoretical accounts of how this takes place, the way in which it occurs in practice through the interaction between therapists and families is not well understood. Adolescent self-harm is one of the most difficult to treat presentations facing mental health professionals today, although family interventions offer a potentially effective way of responding. The present research investigated the processes through which family therapists negotiate the meaning of self-harm during therapeutic conversations taking place over the course of therapy. Method: A grounded theory analysis of video-tapes of family therapy was conducted. Two full cases of family therapy were selected from a pool of tapes recorded as part of an ongoing randomised controlled trial: Self Harm Intervention Family Therapy (‘SHIFT’). A conceptual model of the process through which changes in meaning and relating take place was developed from the analysis of the first case. A second case was selected by means of theoretical sampling and its analysis was used to refine this model. Results: The mutual engagement of family members in therapy was found to be of fundamental importance for the joint exploration of meaning and family relating. Without mutual engagement, other elements of the therapy process are constrained and beneficial change is curtailed. Affect regulation was a prominent theme across the two cases. Discussion: The findings are discussed in the context of the existing literature on functions of self-harm and alliances in family therapy. Implications of the findings for clinical practice are considered and avenues for further research are proposed.