Tumor necrosis factor alpha (TNF alpha) is a proinflammatory cytokine involved in a variety of physiological and pathological conditions. During the past several years substantial progress has been made toward a better understanding of how a single cytokine is able to exert obviously opposing effects (e.g., apoptosis and growth). This review focuses on the recently discovered TNF-receptor (TNFR)-associated proteins involved in the activation of intracellular signal-transduction cascades. It explains which classes of proteins have been described so far and how these factors are able to mediate different biological functions after TNFR activation.