In nature, most bacteria live in close association with surfaces as complex communities referred to as biofilms. Community members within these compact microbial consortia show extraordinary resistance to conventional antibiotics, biocides, and hydrodynamic shear forces when compared to their planktonic counterparts. The buildup of these surface-associated bacterial communities is a highly organized and complex process that requires many signal transduction mechanisms to orchestrate the different stages of development. In this review, we describe several types of signal transduction that Gram-negative bacteria employ during the adhesion and expansion stages of biofilm formation, as well as discuss quorum-sensing in relation to the production of virulence factors.