Numerous studies have demonstrated that patients with dry eyes have a compromised ocular surface. Furthermore, these patients suffer deficiencies of various surface defense mechanisms, such as tear volume, tear components (lysozyme, lactoferrin, and beta-lysin), the mucin network, cellular exfoliation, and subsurface immune secretions. When such individuals wear contact lenses (CLs), a special set of circumstances arises that increases the risk of ocular infection. The risk is greatest if the lenses are soft and, therefore, provide for little tear exchange beneath their surface. Under such circumstances, limited tear flow allows for a greater buildup of lens deposits and metabolic wastes, while permitting increased tear evaporation from the lens surface. The pathogenesis of infection is attributed to various mechanisms, including decreased tear flow beneath the lens, decreased tear components, stagnation of the mucin network, changes in surface cell exfoliation, and putative changes in the subsurface immune secretory system. Dry eye patients who wear soft CLs also run a greater risk of bacterial conjunctivitis, blepharitis, and sterile corneal infiltrates.