Obesity is an increasingly prevalent disease worldwide. While genetic and environmental factors are known to regulate the development of obesity and associated metabolic diseases, emerging studies indicate that innate and adaptive immune cell responses in adipose tissue have critical roles in the regulation of metabolic homeostasis. In the lean state, type 2 cytokine-associated immune cell responses predominate in white adipose tissue and protect against weight gain and insulin resistance through direct effects on adipocytes and elicitation of beige adipose. In obesity, these metabolically beneficial immune pathways become dysregulated, and adipocytes and other factors initiate metabolically deleterious type 1 inflammation that impairs glucose metabolism. This review discusses our current understanding of the functions of different types of adipose tissue and how immune cells regulate adipocyte function and metabolic homeostasis in the context of health and disease and highlights. We also highlight the potential of targeting immuno-metabolic pathways as a therapeutic strategy to treat obesity and associated diseases.