Urinary tract infections (UTIs) are classified by the host condition. Uncomplicated infections are caused most commonly by uropathogenic Escherichia coli (UPEC) and affect otherwise healthy people, whereas complicated infections are commonly caused by species, such as Proteus mirabilis, and affect patients with underlying difficulties, such as a urinary tract abnormality or catheterization. The outcome of infection caused by these bacteria is dictated by the immune response to the UTI and the host factors that influence the susceptibility to disease. This review focuses on the host pathogen interactions in UTI, including an identification of additional virulence factors and therapeutic or prophylactic targets, particularly by UPEC and P. mirabilis.