Introduction: Although clinical practice guidelines (CPG) identify first, second- and third-line mood stabilizer (MS) treatments, they rarely define clinical response to prophylaxis or the core issues to be considered. This project aimed to develop a template for describing how clinical response may be classified and a framework to assist decision-making and monitoring of response in day-to-day practice. Method: A scoping exercise was undertaken followed by narrative synthesis of (a) qualitative and quantitative definitions of MS response applied in clinical and research practice and (b) potential confounders (eg, non-adherence; tolerability issues) of relevance to routine practice, for example, the concepts are applicable to individuals with bipolar disorder for whom sustained remission is a less realistic goal. Expert consensus was employed to develop a taxonomy of response and key concepts that inform clinical judgements about MS response. Results: Five core constructs can be used to systematize clinical judgements regarding MS response and its monitoring: (a) quantitative, qualitative and/or patient-reported outcome measures (PROMS), (b) personalized assessment of the acceptable benefit-to-harm ratio of a proposed treatment, (c) adequacy of treatment exposure (dose, duration, therapeutic monitoring and adherence), (d) illness activity pre- and post-MS initiation, and (e) other potential confounders (co-prescription of MS; polypharmacy) or protective factors (eg, psychosocial factors). Conclusions: This heuristic framework might be used as a teaching aid or by clinicians who wish to take a more systematic approach to developing shared criteria for judging MS response that better match patient expectations and preferences. Heuristic approaches also allow seamless introduction of new evidence.