Bacteria sense and respond to their environment, enabling adaptation to diverse niches, including multicellular eukaryotes. In this issue of Cell Host & Microbe, Torres et al. describe how the bacterium Staphylococcus aureus responds to heme as a molecular marker of the mammalian host environment. It is likely that mechanisms for sensing such markers evolved from systems that recognized cues present in microbial communities before the emergence of eukaryotes.