Nonalcoholic fatty liver disease (NAFLD) is a chronic liver condition characterized by lipid accumulation, inflammation, fibrosis, and cell death. This review highlights the four main types of cell death—apoptosis, necroptosis, pyroptosis, and ferroptosis—and their underlying molecular mechanisms in NAFLD. The article also discusses the effects of cell death-targeted therapies on NAFLD. Apoptosis, the most prevalent form of cell death in NAFLD, is regulated by various pathways and can be influenced by factors such as free fatty acids (FFAs) and lipotoxicity. Necroptosis, an inflammatory form of cell death, is associated with the activation of RIPK1 and RIPK3, leading to plasma membrane rupture and the release of DAMPs. Pyroptosis, a caspase-1-dependent form of cell death, is triggered by the activation of inflammasomes and involves the release of pro-inflammatory cytokines. Ferroptosis, an iron-dependent form of cell death, is characterized by lipid peroxidation and iron overload. The review emphasizes the potential of targeting these cell death pathways as a therapeutic strategy for NAFLD, with several drugs and compounds showing promise in reducing cell death and improving liver function.Nonalcoholic fatty liver disease (NAFLD) is a chronic liver condition characterized by lipid accumulation, inflammation, fibrosis, and cell death. This review highlights the four main types of cell death—apoptosis, necroptosis, pyroptosis, and ferroptosis—and their underlying molecular mechanisms in NAFLD. The article also discusses the effects of cell death-targeted therapies on NAFLD. Apoptosis, the most prevalent form of cell death in NAFLD, is regulated by various pathways and can be influenced by factors such as free fatty acids (FFAs) and lipotoxicity. Necroptosis, an inflammatory form of cell death, is associated with the activation of RIPK1 and RIPK3, leading to plasma membrane rupture and the release of DAMPs. Pyroptosis, a caspase-1-dependent form of cell death, is triggered by the activation of inflammasomes and involves the release of pro-inflammatory cytokines. Ferroptosis, an iron-dependent form of cell death, is characterized by lipid peroxidation and iron overload. The review emphasizes the potential of targeting these cell death pathways as a therapeutic strategy for NAFLD, with several drugs and compounds showing promise in reducing cell death and improving liver function.