Millions of people worldwide are blinded due to cataract formation. At present the only means of treating a cataract is through surgical intervention. A modern cataract operation involves the creation of an opening in the anterior lens capsule to allow access to the fibre cells, which are then removed. This leaves in place a capsular bag that comprises the remaining anterior capsule and the entire posterior capsule. In most cases, an intraocular lens is implanted into the capsular bag during surgery. This procedure initially generates good visual restoration, but unfortunately, residual lens epithelial cells undergo a wound-healing response invoked by surgery, which in time commonly results in a secondary loss of vision. This condition is known as posterior capsule opacification (PCO) and exhibits classical features of fibrosis, including hyperproliferation, migration, matrix deposition, matrix contraction and transdifferentiation into myofibroblasts. These changes alone can cause visual deterioration, but in a significant number of cases, fibre differentiation is also observed, which gives rise to Soemmering's ring and Elschnig's pearl formation. Elucidating the regulatory factors that govern these events is fundamental in the drive to develop future strategies to prevent or delay visual deterioration resulting from PCO. A range of experimental platforms are available for the study of PCO that range from in vivo animal models to in vitro human cell and tissue culture models. In the current review, we will highlight some of the experimental models used in PCO research and provide examples of key findings that have resulted from these approaches.