Abstract: Bacteriophages (“phage”) are viruses that exclusively infect bacteria and therefore are promising alternatives to antibiotics in eliminating biofilms. However, the interaction of phage with biofilm structure remains underexplored. We have shown that, in Pseudomonas aeruginosa biofilms, lytic phage can induce a dramatic rearrangement of the rod-shaped cells into ordered, laterally aligned “stacked” aggregates. This is due to the entropic depletion force, which arises from the exclusion of smaller particles from the vicinity of bacterial cells. Critically, as phage infect and lyse cells, progeny phage and biopolymers accumulate in the extracellular space, eventually attaining the densities required for the depletion force to operate. This phenomenon poses a novel problem for phage therapy: the very agent used to destroy infecting bacteria may instead promote their flourishing by restructuring surviving cells into phage-resistant aggregates. In this talk, I will identify the conditions under which phage-induced aggregation occurs and discuss their relevance to human infections. I will then provide evidence that stacked aggregates confer greater protection from phage than the typical biofilm environment.