About 5.48 million people are estimated to suffer from severe traumatic brain injury (TBI) each year (73 cases per 100,000 people). The WHO estimates that almost 90% of deaths due to injuries occur in low- and middle-income countries (LMICs), where the 85% of population live. Of these trauma-related deaths TBI is the main cause of one-third to one-half and represents the greatest cause of death and disability globally among all trauma-related injuries. The primary causes of TBI vary by age, socioeconomic factors, and geographic region, so any planned interventions must take in account this variability. The road traffic injuries (RTI) scenario is still strictly connected to the analysis of the global incidence of TBI, and to the reason why the LMICs experience nearly 3 times as many cases of TBI proportionally than high-income countries (HICs). The proportion of TBIs resulting from road traffic collisions was greatest in Africa and Southeast Asia (both 56%) and lowest in North America (25%). In HICs, falls and RTIs were reported most frequently as cause of TBI, but the traumas attributable to RTIs dropped from 39% in 2003 to 24% in 2012, while those attributable to falls increased from 43% to 54% respectively, with an increase TBI in the elderly (>65 years) due to falls. Differently from HICs, the population with the peak of TBI incidence is younger in LMICs, with an age between 28.8 and 33.1, as extensively reported. The burden of disease is significant; between 1,730,000 and 1,965,000 lives could be saved if global trauma care were improved in LMICs. Clinical practice recommendation should be developed and created in environments where the severe TBI mainly occurs. The applicability of high-income-country clinical research standards in LMICs is an important topic for future international research.