Many normal physiological and disease-related pathophysiological processes are regulated by the interactions of complex signaling networks of pro-and anti-inflammatory markers, growth factors, soluble receptors and extracellular matrix proteins, as well as other cell-cell signaling proteins, which we define collectively as cytokines. Because multiple cell-cell signaling factors may be involved in a single biological process, detection of expression of multiple cytokines is essential to unraveling the mechanisms and effects of many disease processes. Cytokine antibody arrays have been developed to meet this growing demand for multiplexed protein detection. In particular, discovery and validation of diseaserelated protein biomarkers require high-throughput detection of many proteins simultaneously. This review will address the complexity of cytokine biology, discuss current and future antibody array technologies and explore their applications in cytokine biomarker discovery and validation for variety of human diseases. Specific examples of these applications will be presented, including the search for cytokine biomarkers related to neurological and neurodegenerative diseases (such as autism and Alzheimer's), immunological disorders (including asthma), and various cancers.