Traumatic brain injury is a serious clinical problem connected with high mortality rate and long-term neurobehavioral and socioeconomic consequences. Pathomechanism of such insult is complex and not clear in all aspects as yet. Thus, a primary mechanistic insult to the brain initiates metabolic and inflammatory processes which exacerbate the primary traumatic injury to neurons, leading to secondary brain damage. In this paper we present the main components of destructive cascade with relevant theoretical strategy for neuroprotection. It should be emphasized that pathological processes involved in secondary brain damage are complex and interrelated. It makes blockade of a single mechanism unlikely to prevent either early or delayed cellular death.