Pseudoexfoliation syndrome (PES) is a common age-related disorder affecting 60–70 million people worldwide. Patients with PES have abnormal production and deposition of fibrillar material in the anterior chamber of the eye. These exfoliated fibrils, easily detected by ocular slit-lamp examination, have also been found to exist systematically in the skin, heart, lungs, liver and kidneys. Recently, myriad studies have associated PES with systemic conditions such as increased vascular risk, risk of dementia and inflammatory state. We review here the most current literature on the systemic implications of PES. Our aim is to encourage further studies on this important clinical entity.