Current medicine has a high level of interest in studies of the pathogenesis of traumatic brain injury (TBI). This comes particularly from high levels of hospitalization of patients with this pathology, its high mortality, and the low level of development of existing treatment methods. Improvements in the understanding of the pathogenesis of TBI require appropriate experimental designs, starting with suitable selection of animal models. Zebrafish (Danio rerio) have been identified as a potential organism for studying the molecular events underlying the pathogenesis of TBI. The advantages of this model organism include a high level of genetic homology with humans, relatively low costs, and high neuroregenerative potential. The pathogenesis of TBI involves multiple processes: the primary traumatic damage, neuroinflammation, neurodegeneration, cerebral edema, and neuroregeneration. Many important events related to these processes have been well-studied in rodent models. However, the molecular processes of TBI pathogenesis remain poorly understood. This review addresses experimental models of TBI in zebrafish and discusses their advantages and limitations, as compared with other model organisms. The review also examines the pathophysiology and molecular biology underlying the pathogenesis of TBI. Several examples of the experimental therapy of TBI in zebrafish are presented, reflecting the potential for future developments in this field, and emphasizing the value of zebrafish as a model object for studying TBI pathogenesis.