Novel high-throughput biological applications in the drug discovery process, disease diagnosis, and the development and application of patient-specific medicines require highly parallel, miniaturized device technology applied to proteins and their biochemical pathways. While technological innovation has adapted the analysis of genetic material to a miniaturized format, the more delicate nature of protein structures has precluded the development of analogous devices for proteins. Protein biochips have started to emerge recently based on new developments and integration efforts in advanced materials, protein engineering, and detection physics. Recent developments and selected examples will be presented with an emphasis on the technical challenges in surface and assay methodologies.