Tumor necrosis factor is important in systemic and cutaneous defense, homeostasis, and many disease states. The numerous and diverse effects of tumor necrosis factor are best understood when considered as concentration-dependent, with normal homeostasis progressing to defense followed by toxic effects. Understanding tumor necrosis factor is important for the dermatologist as more studies appear in our literature and potential clinical uses of tumor necrosis factor (and possible anti-tumor necrosis factor agents) are realized.