This review will examine the current situation with label-free, quantitative, shotgun-oriented proteomics technology and discuss the advantages and limitations associated with its capability in capturing and quantifying large portions of proteomes of microorganisms. Such an approach allows (1) comparisons between physiological or genetic states of organisms at the protein level, (2) 'painting' of proteomic data onto genome data-based metabolic maps, (3) enhancement of the utility of genomic data and finally (4) surveying of non-genome sequenced microorganisms by taking advantage of available inferred protein data in order to gain new insights into strain-dependent metabolic or physiological capacities. The technology essentially is a powerful addition to systems biology with a capacity to be used to ask hypothesis-driven 'top-down' questions or for more empirical 'bottom-up' exploration.