Abstract The availability of the confocal microscope over the past decade has allowed clinicians and researchers to refine their understanding of the physiological and pathological basis of the ocular response to contact lens wear, and to discover previously unknown phenomena. Mucin balls, which form in the tear layer in patients wearing silicone hydrogel lenses, can penetrate the full thickness of the epithelium, leading to activation of keratocytes in the underlying anterior stroma. Epithelial cell size increases in response to all forms of lens wear, with lenses of higher oxygen transmissibility (Dk/ t) interfering least with the normal process of epithelial desquamation. A higher density of Langerhans’ cells is observed in the layer of the sub-basal nerve plexus among contact lens wearers, suggesting that contact lens wear may be altering the immune status of the cornea. Dark lines and folds are observed in the oedematous cornea in response to contact lens wear. Mechanical stimulation of the corneal surface, due to the physical presence of a contact lens, and the consequent release of inflammatory mediators, is the likely cause of reduced keratocyte density associated with lens wear. Highly reflective stromal ‘microdot deposits’ are observed throughout the entire stroma in higher numbers in lens wearers. ‘Blebs’ in the endothelium have a bright centre surrounded by a dark annular shadow; this appearance is explained with the aid of an optical model. The confocal microscope has considerable clinical utility in diagnosing Acanthamoeba and fungal keratitis. At the limbus, contact lenses can induce structural changes such as increases in basal epithelial cell size. An increased number of rolling leucocytes is observed in limbal vessels in response to low Dk/ t lenses. It is concluded that the confocal microscope has considerable utility in contact lens research and practice.