Given the many evidence-supported psychotherapy interventions, and the fact that no single approach or therapist can successfully help all patients, in recent years, there has been a surge in studies focused on evidence-based methods of tailoring treatment to patients, providers, and processes. Although the field still has a long way to go in reliably mapping specific empirically supported avenues to personalized therapies, emerging results from this line of research underscore the potential for such optimization. In this vein, the articles in the special issue describe some of the most auspicious recent developments in the field of personalized mental health treatment. In this introduction to the special issue, we synthesize the articles and propose a list of some of the most promising personalization principles. These include (a) a diversity of aims that the approaches seek to achieve; (b) a diversity of outcomes used to evaluate the merits of these approaches; (c) the information on which the tailoring is based; (d) the tailoring approaches themselves; and (e) the research designs used to evaluate them. These pathways can inform the most current tailoring guidelines that can help clinical decision-making and inspire future translational science in this area. (PsycInfo Database Record (c) 2022 APA, all rights reserved)