The major classes of cytokines include: pro- and anti-inflammatory cytokines, cytokines of neutrophil and eosinophil recruitment and activation, cytokines derived from T-helper (Th) and T-regulatory (Tregs) cells, and cytokines of T-cell recruitment and growth factors. Cytokines are peptides that have a fundamental role in communication within the immune system and in allowing the immune system and host tissue cells to exchange information. Cytokines act via binding to a receptor that in turn sends a signal to the recipient cell, leading to a change in function or phenotype. Such signal cascades are complex and integrate a variety of environmental factors. Cytokines exist in broad families that are structurally related but exhibit diverse function (e.g., the TNF/TNF receptor superfamily, interleukin [IL]-1 superfamily, and IL-6 superfamily). Cytokine targeting has proven effective in many rheumatic diseases, particularly therapeutics that inhibit TNF or IL-6. Many more cytokines are currently under investigation as therapeutic targets or as therapeutic agents.