Antibodies represent the end product of an exquisitely complex biological process including recombination, somatic hypermutation, affinity maturation, and self-tolerance, culminating in binding reagents directed against a vast repertoire of antigens. The resultant high affinity and diversity of specificity of these biomolecules has been exploited through the development of immunoassays and biotherapeutics that inaugurated a new era in experimental molecular biology and pharmaceutical drug development. Despite the utility of antibodies for research applications and in disease treatment, they must be employed in the context of an accurate understanding of their binding profile. High-content microarrays comprised of thousands of native, full length human proteins are an important tool in the assessment of antibody specificity.