A unique approach to the treatment of posttraumatic stress disorder (PTSD) is difficult to support, because of the complexity and heterogeneity of this pathology. Multiple evidence-based guidelines for PTSD treatment exist, elaborated by prestigious institutions around the world, but a certain level of the inconsistency of their recommendations appears when these sources are compared with each other. Therefore, a review of current guidelines and extraction of the most supported by evidence recommendations is considered important for clinical practice, due to the need to approach such complex cases as PTSD-diagnosed patients in a stepwise manner. Structured monitoring of the clinical status during the treatment is also an important and rather neglected aspect of the case management in PTSD, and the necessity of follow-up visits for efficacy and tolerability should be taken into consideration. Psychotherapy (especially cognitive- behavioral oriented therapies and eye movement desensitization and reprocessing therapy) is supported by evidence as a first-line approach, as well as certain antidepressants, like the selective serotonin reuptake inhibitors and venlafaxine. Many second-line pharmacological agents and psychotherapies are also available, but there is an obvious need for more pragmatic trials with PTSD patients.