Recent progress in the field of neurobiology supported by clinical evidence gradually reveals the mystery of human brain functioning. So far, many psychiatric disorders have been described in great detail, although there are still plenty of cases that are misunderstood. These include posttraumatic stress disorder (PTSD), which is a unique disease that combines a wide range of neurobiological changes, which involve disturbances of the hypothalamic-pituitary-adrenal gland axis, hyperactivation of the amygdala complex, and attenuation of some hippocampal and cortical functions. Such multiplicity results in differential symptomatology, including elevated anxiety, nightmares, fear retrieval episodes that may trigger delusions and hallucinations, sleep disturbances, and many others that strongly interfere with the quality of the patient's life. Because of widespread neurological changes and the disease manifestation, the pharmacotherapy of PTSD remains unclear and requires a multidimensional approach and involvement of polypharmacotherapy. Hopefully, more and more neuroscientists and clinicians will study PTSD, which will provide us with new information that would possibly accelerate establishment of well-tolerated and effective pharmacotherapy. In this review, we have focused on neurobiological changes regarding PTSD, addressing the most disturbed brain structures and neurotransmissions, as well as discussing in detail the recently taken and novel therapeutic paths.