Today's proteomic analyses are generating increasing numbers of biomarkers, making it essential to possess highly specific probes able to recognize those targets. Antibodies are considered to be the first choice as molecular recognition units due to their target specificity and affinity, which make them excellent probes in proteomics. In the post-genomic era and with high-throughput techniques available, the goal is to discriminate between all individual proteins from the proteome including their splice variants and post-translationally modified derivatives. Aided by advances in generation, selection and engineering of antibody-based recognition units, antibody fragments provide tools for detection of high- as well as low-abundant analytes even in complex, non-fractionated proteomes in conjunction with usage of small amounts of samples and reagents. In addition, large consortia aim at generating vast numbers of antibody-based recognition units suitable for future diagnostics and therapeutics.