Prokaryotes are thought to regulate their proteomes largely at the level of transcription. However, the results from this first set of global transcriptomic and proteomic analyses of paired microbial samples presented here show that this assumption is false for the majority of genes and their products in S. pyogenes . In addition, the tenuousness of the link between transcription and translation becomes even more pronounced when microbes exist in a biofilm or a stationary planktonic state. Since the transcriptome level does not usually equal the proteome level, the validity attributed to gene expression studies as well as proteomic studies in microbial analyses must be brought into question. Therefore, the results attained by either approach, whether RNA-seq or shotgun proteomics, must be taken in context and evaluated with particular care since they are by no means interchangeable.