Insulin is a polypeptide hormone synthesized and secreted by pancreatic β-cells, playing a crucial role in regulating glucose metabolism and various metabolic processes. It influences glucose storage in organs like the liver, muscles, and adipose tissue, and is involved in fat metabolism, ketone body metabolism, and protein metabolism. Insulin resistance (IR) is characterized by decreased responsiveness of insulin-sensitive tissues to insulin, leading to hyperinsulinemia and impaired metabolic processes. This review discusses the mechanisms of insulin resistance, its causes, types, and associated syndromes, focusing on cellular changes in response to IR. The review also covers the biosynthesis and secretion of insulin, intracellular insulin signaling pathways, and the role of insulin in various cells, tissues, and organs. Severe insulin resistance syndromes, such as Donohue syndrome and Rabson-Mendenhall syndrome, are discussed, along with other rare genetic syndromes associated with IR. The mechanisms of IR, including defects in insulin signaling pathways, lipodystrophies, and the glucose-fatty acid cycle, are explored. The review highlights the impact of IR on metabolic diseases, cancer, and cognitive function, emphasizing the need for further research to understand and manage this condition.Insulin is a polypeptide hormone synthesized and secreted by pancreatic β-cells, playing a crucial role in regulating glucose metabolism and various metabolic processes. It influences glucose storage in organs like the liver, muscles, and adipose tissue, and is involved in fat metabolism, ketone body metabolism, and protein metabolism. Insulin resistance (IR) is characterized by decreased responsiveness of insulin-sensitive tissues to insulin, leading to hyperinsulinemia and impaired metabolic processes. This review discusses the mechanisms of insulin resistance, its causes, types, and associated syndromes, focusing on cellular changes in response to IR. The review also covers the biosynthesis and secretion of insulin, intracellular insulin signaling pathways, and the role of insulin in various cells, tissues, and organs. Severe insulin resistance syndromes, such as Donohue syndrome and Rabson-Mendenhall syndrome, are discussed, along with other rare genetic syndromes associated with IR. The mechanisms of IR, including defects in insulin signaling pathways, lipodystrophies, and the glucose-fatty acid cycle, are explored. The review highlights the impact of IR on metabolic diseases, cancer, and cognitive function, emphasizing the need for further research to understand and manage this condition.