Natural killer (NK) cells, traditionally considered innate immune cells, are now recognized for their capacity to develop memory-like responses under certain conditions. These memory-like NK (ML NK) cells demonstrate enhanced and prolonged responses upon secondary encounter with an antigen or a stimulus. By mirroring memory T and B cells, they challenge the traditional view of NK cells as purely innate, short-lived cells. ML NK cells have been observed with certain viral infections (also called adaptive NK cells), hapten-induced contact hypersensitivity, and cytokine stimulation (also called cytokine-induced memory-like or CIML NK cells), indicating diverse stimuli can induce their differentiation. Mechanisms underlying ML NK cell development involve epigenetic modifications, transcriptional regulation, and altered metabolism, leading to distinct functional and phenotypical characteristics. ML NK cells display enhanced effector functions including increased cytokine production, cytotoxicity, proliferation, and survival. Investigating the molecular pathways governing ML NK cell differentiation and maintenance is crucial for developing novel immunotherapies against cancer. This chapter provides a comprehensive overview of ML NK cells, outlining their biological characteristics and underlying mechanisms. It includes species-specific comparisons between human and murine ML NK cells, examines their translational potential in clinical settings, and summarizes key past and ongoing clinical trials.