Despite increased empirical support for, and consensus recognition of, the values of responsive treatment personalization in the delivery of evidence-based mental health care for youth, the literature has actually offered very little structured guidance with which to inform the actual practice of treatment flexibility. The present paper offers aworking heuristic framework for navigating the necessary deliberations that must be at the center of individual therapist efforts to thoughtfully tailor evidence-based practices. Our guiding Strategic Flexibility Model is organized around five critical questions/deliberations, which we collectively refer to as "the Who, What, When, Where, and Why of Strategic Flexibility." Specifically, our model has the therapist thoughtfully consider: (1) who warrants treatment flexibility?; (2) what treatment components merit flexibility, and what modifications can be applied?; (3) when in treatment is flexibility warranted?; (4) where (i. e., in what settings) is flexibility needed, and where (in what settings) can flexibility by applied?; and (5) why (i.e., to what end) should flexibility be applied under specific circumstances? Strategic Flexibility is conceptualized as an active and dynamic process of careful consideration, hypothesis generation, hypothesis testing, and course correction, as needed. Within our model, it is haphazard clinical "off-roading"-not protocol non-adherence, per say-that is of primary concern. Specific examples are offered throughout, and recommendations for future efforts on this front are discussed.