The chapter discusses the metabolic regulation of the immune system in health and diseases, focusing on the mechanisms and interventions. Metabolism, including glycolysis, oxidative phosphorylation, and fatty acid oxidation, plays a crucial role in the phenotypes and functions of immune cells. The concept of immunometabolism, introduced over a decade ago, highlights the intricate interplay between metabolism and immunity. This concept has expanded from chronic low-grade inflammation in metabolic diseases to metabolic reprogramming of immune cells in various diseases. The chapter explores the metabolic pathways and reprogramming in different immune cell types, such as macrophages, T cells, B cells, neutrophils, and dendritic cells. It also discusses the impact of metabolic regulation on immune cell functions in the context of diseases, including cancer, autoimmune diseases, and metabolic diseases. The chapter emphasizes the potential of targeting cellular metabolism of immune cells as a promising therapy and reviews existing studies on immunometabolism, while also addressing the challenges in translating experimental results into clinical applications.The chapter discusses the metabolic regulation of the immune system in health and diseases, focusing on the mechanisms and interventions. Metabolism, including glycolysis, oxidative phosphorylation, and fatty acid oxidation, plays a crucial role in the phenotypes and functions of immune cells. The concept of immunometabolism, introduced over a decade ago, highlights the intricate interplay between metabolism and immunity. This concept has expanded from chronic low-grade inflammation in metabolic diseases to metabolic reprogramming of immune cells in various diseases. The chapter explores the metabolic pathways and reprogramming in different immune cell types, such as macrophages, T cells, B cells, neutrophils, and dendritic cells. It also discusses the impact of metabolic regulation on immune cell functions in the context of diseases, including cancer, autoimmune diseases, and metabolic diseases. The chapter emphasizes the potential of targeting cellular metabolism of immune cells as a promising therapy and reviews existing studies on immunometabolism, while also addressing the challenges in translating experimental results into clinical applications.