Glaucoma management may be extremely challenging, especially in elderly patients who have a variety of systemic diseases and take multiple medications. We obtained a comprehensive medical history in patients with primary open-angle glaucoma to determine which systemic diseases are most prevalent and which systemic medications are most commonly used. We have also reviewed the literature that addresses how these concomitant diseases and medical treatments influence the management of glaucoma. Knowledge of systemic diseases and potential drug interactions, especially between various systemic and glaucoma medications, is important for the safe management of glaucoma patients.