Psychotherapy, especially cognitive behavioral therapy, is the first-line treatment of post-traumatic stress disorder (PTSD) and other trauma-related disorders. Despite this fact, pharmacological treatment options are commonly used in clinical practice for the alleviation of PTSD symptoms or treatment of comorbidities due to personal preferences or due to the lack of availability of psychotherapy, for example, for patients with limited language proficiency. Therefore, this chapter reviews current evidence as well as national and international guidelines for pharmacological treatment of PTSD. Despite the common practice of prescribing antidepressants, antipsychotics, mood stabilizers, and a variety of other medications, evidence for the benefit of medication for trauma-related disorders remains relatively weak. Only a few medications are officially on-label for PTSD (paroxetine, sertraline), while others have shown beneficial effects but to date remain off-label treatments, such as venlafaxine. A number of novel treatment approaches, for example, including antiadrenergic medications or psychedelic drugs, have yet to demonstrate a clear clinical benefit. Due to the fact that the benefit of medication for the treatment of trauma-related disorders remains limited, care for patients with trauma-related disorders should focus on psychotherapeutic strategies.