Glaucoma, the second leading cause of irreversible blindness globally, encompasses a heterogeneous group of ocular disorders characterized by the progressive degeneration of retinal ganglion cells. Pharmacotherapy remains the cornerstone of treatment, primarily aimed at reducing intraocular pressure (IOP) by decreasing aqueous humor production or enhancing its outflow. The therapeutic classes employed include carbonic anhydrase inhibitors, β-blockers, α-adrenergic agonists, prostaglandin analogs, parasympathomimetics, Rho kinase inhibitors, and hyperosmotic agents. Despite their efficacy, these medications are associated with a range of ocular and systemic side effects, influenced by their mechanisms of action, formulation, and dosage. Ocular adverse effects, such as irritation, dry eye, allergic reactions, and infections, are common, while systemic absorption may lead to more severe outcomes, including organ dysfunction, exacerbation of comorbid conditions, or life-threatening cardiovascular events. Given these potential risks, it is critical for clinicians to understand and monitor these adverse effects, as they significantly affect patient adherence, quality of life, and treatment outcomes. Ongoing research is essential to develop novel therapeutic regimens, agents, or delivery methods that minimize side effects and improve compliance. Incorporating patient-reported outcomes in clinical practice may further enhance the assessment of treatment impact, facilitating more tailored and effective management of glaucoma.