This review examines the role of programmed cell death in the pathogenesis of obesity and associated conditions. It provides the comprehensive examination of the key mechanisms of apoptosis and NETosis in the context of the pathogenesis of obesity and associated metabolic diseases, particularly type 2 diabetes mellitus, dyslipidemia, and metabolic dysfunction-associated steatotic liver disease (MASLD). One of the key consequences of excessive adipose tissue accumulation in obesity is chronic low-grade inflammation. The development of a proinflammatory state, the resulting cellular stress, and mitochondrial dysfunction contribute to the activation of signaling pathways that trigger programmed cell death. Apoptosis of adipocytes, cardiomyocytes, endothelial cells, pancreatic β-cells, and hepatocytes is mediated by an imbalance of proand antiapoptotic proteins of the Bcl-2 family and caspase activation and is implicated in the development of MASLD, type 2 diabetes mellitus, diabetic cardiomyopathy, and endothelial dysfunction. Studies of potentially protective molecules (apelin-13, agomelatine) and triggers are described. NETosis plays a key role in maintaining inflammation, endothelial dysfunction, and the development of thrombotic complications in obesity. Increased activity of NETosis markers, myeloperoxidase and neutrophil elastase, correlates with the severity of obesity, MASLD, and microvascular complications, while their inhibition restores endothelial function in preclinical models. Thus, key molecular factors and signaling pathways of apoptosis and NETosis are significant components in the pathogenesis of obesity and associated diseases. Studying the mechanisms of programmed cell death is a promising area in the context of the search for potential therapeutic targets for these diseases.