Bacteria must sense and respond to their environment by modulating signaling pathways and phenotypes to maximize survival. Heme proteins play roles in sensing the bacterial environment and controlling the switch between motile and sessile (biofilm) states. Globin coupled sensors are heme proteins that consist of a globin domain linked by a central domain to an output domain, such as diguanylate cyclase domains that synthesize c-di-GMP, a major regulator of biofilm formation. Characterization of globin coupled sensor proteins has elucidated the effects of heme ligand binding on catalysis and protein oligomerization, as well as the downstream effects on bacterial phenotypes, such as virulence and biofilm formation. Given that bacteria form biofilms in response to numerous signals and that biofilms are linked to bacterial infections, it is important to understand the myriad small molecules and pathways controlling biofilm formation. My group has identified additional nucleotides, 2’,3’-cyclic nucleotide monophosphates, as products of mRNA degradation that are involved in modulating biofilm formation and motility. The enzyme responsible for 2’,3’-cNMP production has been identified and current studies are identifying other proteins involved in 2’,3’-cNMP metabolism and sensing. Taken together, our work provides insight into new proteins and small molecules involved in biofilm formation and motility, as well as highlights new bacterial signaling pathways.