Increasing experimental evidence indicates that several factors that influence metabolism also play a role in the regulation of immune responses. Dissection of the interface connecting the metabolic and immune systems has recently gained wide interest. Particular focus has been on certain cytokines [interleukin-1 (IL-1), IL-6, tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma)], hormones (leptin and insulin), neuropeptides (corticotropin-releasing hormone and alpha-melanocyte-stimulating hormone), immune-related proteins (zinc-alpha2-glycoprotein and attractin and/or mahogany), transcription factors (peroxisome-proliferator-activated receptors) and glucose metabolism. A better knowledge of the intricate network of interactions among energy regulation, immune surveillance and vital organ functions could in the near future lead to valuable strategies for therapeutic intervention in several immune-mediated diseases.