Objective: There exists considerable individual variability in the development and progression of pathological stress reactions after experiencing trauma, as well as in individuals’ response to psychological interventions. Yet until recently, such individual differences had not been considered when evaluating the efficacy of therapeutic interventions for post-traumatic stress disorder (PTSD). This systematic review aims to examine the emerging literature on this subject and, specifically, to identify trajectories and predictors of psychotherapeutic response in adults with PTSD. Method: Four databases were searched using specific keywords without date or language restrictions. For each study, independent reviewers systematically evaluated whether it met eligibility criteria and assessed risk of bias. For included studies, reviewers completed data extraction using standard formats. Those examining how subgroups of adults respond to therapy for clinical PTSD using trajectory modeling were deemed eligible. Demographic, PTSD, clinical, and trauma-related factors associated to particular trajectories were also examined. Results: Of the 1,727 papers identified, 11 were included in this analysis. Of these studies, six focused on military-related traumas and five on civilian ones. Although studies found between two and five trajectories, most supported a three-trajectory model of response categorized as responders, nonresponders, and subclinical participants. Over 22 predictors of treatment trajectories were examined. Comorbid depression, anxiety, and alcohol abuse were the strongest predictors of poor therapeutic response. Age, combat exposure, social support, and hyperarousal were moderate predictors. Conclusion: This review provides valuable insight into the treatment of PTSD, as it supports the heterogeneous trajectories of psychotherapeutic responses and provides avenues for the development of interventions that consider individual-level factors in treatment response.