Microarrays are powerful tools in biomedical research and have become indispensable for high-throughput multiplex analysis, especially for DNA and protein analysis. The basis for all microarray processing and fabrication is surface modification of a chip substrate and many different strategies to couple probe molecules to such substrates have been developed. We present here a critical assessment of typical biochip generation processes from a surface science point of view. While great progress has been made from a molecular biology point of view on the development of qualitative assays and impressive results have been obtained on the detection of rather low concentrations of DNA or proteins, quantitative chip-based assays are still comparably rare. We argue that lack of stable and reliable deposition chemistries has led in many cases to suboptimal quantitative reproducibility, impeded further progress in microarray development and prevented a more significant penetration of microarray technology into the diagnostic market. We suggest that surface-attached hydrogel networks might be a promising strategy to achieve highly sensitive and quantitatively reproducible microarrays.