Assays built upon protein arrays are critical tools in determining the basic nature of biology, and have considerable promise in diagnosing human disease. These protein arrays aid in the elucidation of mapping pathway interactions, disease biomarker discovery, and regulatory processes. The solutions used in these experiments, including cellular lysate and serum, are inherently complex mixtures and are high in total protein content. Therefore, array-based assays must be robust and maintain a high level of selectivity and sensitivity. We report herein that arrayed imaging reflectometry (AIR), a label-free biosensing platform we have previously disclosed, is highly suitable for the detection of human proteins in complex solutions. In particular, we demonstrate array-based detection of cytokines in buffered solutions, and in undiluted human serum.