Glaucoma affects millions of people around the world. With the baby boom generation aging, the number of people affected by primary open-angle glaucoma in the US is expected to reach 3.3 million by 2020, and about half may not know they have the disease. The treatment of most forms of glaucoma includes the use of topical agents that enhance aqueous humour outflow, reduce aqueous production, or both. Topical intraocular pressure-lowering drugs must penetrate across the tissues of the eye to reach their therapeutic targets. Often, these tissues show the first signs and symptoms of drug toxicity and adverse effects. These include eyelid dermatitis, malpositions, lacrimal system scarring, ocular discomfort upon instillation, tear film instability, conjunctival inflammation, subconjunctival fibrosis, conjunctival epithelium changes, and corneal surface and endothelial impairment. For these reasons, ophthalmologists should evaluate the risks and benefits of ophthalmic medications before initiating therapy, identify the minimum dosages necessary to achieve a therapeutic benefit, and monitor patients for local and systemic adverse effects. Adverse events may be reduced by changing to a different class of topical medication, using corticosteroids, lubricating the eyes frequently, and reducing exposure to preservatives. This in turn can lead to higher levels of adherence to antiglaucoma therapy, improved outcomes and a reduction in the costs associated with long-term glaucoma complications. This article reviews the ocular adverse effects associated with the various classes of topical antiglaucoma drugs, with a particular focus on the ocular surface, eyelids and periorbital tissue.