Malignant brain tumors, which are characterized by their aggressive and destructive nature, invasive growth, and high morbidity and mortality rates, pose significant challenges for researchers striving to develop effective treatment strategies. Although advancements in chemotherapy, radiation, and neurosurgery have improved patient prognosis, certain malignancies, such as high-grade gliomas and medulloblastoma, still exhibit poor outcomes due to disease recurrence and progression. In recent years, natural killer (NK) cells, a dominant subcategory of innate immune cells, have emerged as key players in antitumor immunity, including in brain tumors. The release of cytotoxic molecules and cytokines enables NK cells to display strong antitumor effects. Consequently, NK cell immunotherapy has gained attention as a promising therapy for brain tumors. This chapter provides a comprehensive exploration of NK cells from a biological perspective and their pivotal role within the immune microenvironment of brain tumors. Furthermore, this chapter highlights the significance of NK cells in inducing antitumor immune responses and emphasizes their potential as therapeutic agents in preclinical studies. The chapter also discusses strategies to augment the tumor-fighting capabilities of NK cells. Furthermore, it investigates the impact of NK-cell-based therapies on patients diagnosed with glioblastoma and other brain tumor types. Furthermore, this chapter addresses the challenges that hinder the advancement of NK cell therapy against brain tumors.