Biological systems are dynamic, they constantly respond to internal and external signals. In multicellular organisms, cells are affected by changes to the conditions being experienced locally by an organ or organism as a whole. Many of the signals are transmitted by changes in the concentration or activity of proteins. Sometimes certain proteins can even appear in the proteome or disappear from the proteome. If cellular dynamics are to be understood, it is necessary to develop methods that analyse the changes in the proteome in response to external signals, such as the release of insulin after a meal, and changes that occur internally as a result of processes like the cell cycle. This will require the analysis of many time points and samples, which will only be achieved through the application of robust automated methods.The use of isotope-coded affinity tagging (ICAT) and mass spectrometry as a means to address quantitative proteome analysis has attracted much interest, however, the complexity of the method with its many steps make it difficult to apply on a large scale. Zhou et al. have presented a new way to approach this promising technique [1xQuantitative proteome analysis by solid-phase isotope tagging and mass spectrometry. Zhou, H. et al. Nat. Biotechnol. 2002; 20: 512–515Crossref | PubMed | Scopus (318)See all References][1]. The peptide-labelling and affinity-capture steps have been combined into a single solid-phase reaction. This not only improves the kinetics of the labelling reaction but also reduces the amount of sample handling leading to improved sensitivity through less sample loss. The label has also been designed to be photo-cleavable, resulting in a mass tag of only 170 Da, which is much smaller than the original ICAT label, and generating mass spectra that are not complicated by fragmentation of the label in the mass spectrometer. The chemistry used in the process is based on well established solid-phase peptide synthesis methods and so could lead to numerous other labelling strategies that permit the capture of peptides other than those containing cysteine resides. This is an important consideration because not all protein molecules contain cysteines. Finally, the use of solid-phase chemistry opens up the way for the automation of the process and a consequent significant increase in sample throughout and reproducibility.As we learn more about which proteins interact in cells, many new questions will arise. Knowing that two or more proteins interact, to say transmit a signal, though useful, will not explain the dynamics at the heart of the process. To reach this level of understanding, we must determine, when the signal is sent, how strong it is and what are the effects it exerts. These questions all require quantitative information as well as rigorous multiple experiments. The new availability of reagents like ICAT (http://www.appliedbiosystems.com/products/productdetail.cfm?prod_id=153) are a starting point for quantitative systems biology. To turn on a light bulb it's not enough to flick the switch unless the power generation systems, the transmission system and the final voltage are all set at the right level. Similarly, to truly understand how proteins function we must understand when and where they are up or down regulated.