The definition of the role of each gene product in its cellular context is of outstanding importance in the post-genomics era. Recent technological innovations have driven research in proteomics from single protein characterization to global approaches, aiming to achieve a comprehensive qualitative and quantitative description of complex molecular mechanisms. In this review, we discuss the methodology of quantitative proteomics as it applies to the analysis of complex biological model systems. A special attention will be given to model systems that are suitable for functional genomic studies, where the potential of quantitative proteomics can be effectively demonstrated.