Biomaterials may be defined as artificial materials that can mimic, store, or come into close contact with living biological cells or fluids and are becoming increasingly popular in the medical, biomedical, optometric, dental, and pharmaceutical industries. Within the ophthalmic industry, the best example of a biomaterial is a contact lens, which is worn by ∼125 million people worldwide. For biomaterials to be biocompatible, they cannot illicit any type of unfavorable response when exposed to the tissue they contact. A characteristic that significantly influences this response is that related to surface wettability, which is often determined by measuring the contact angle of the material. This article reviews the impact of contact angle on the biocompatibility of tissue engineering substrates, blood-contacting devices, dental implants, intraocular lenses, and contact lens materials.