INTRODUCTION: Several large, randomized, prospective clinical trials have demonstrated that medical therapy to reduce intraocular pressure (IOP) delays the onset and decreases progression of glaucoma. Many patients with glaucoma require more than one ocular hypotensive medication to achieve and maintain their target IOP; however, use of multiple topical glaucoma preparations is associated with factors that may decrease treatment efficacy and increase adverse effects.AREAS COVERED: This article reviews the use of fixed-combination therapies in glaucoma management, the relationship between IOP management and disease progression and challenges associated with glaucoma therapy when multiple instillations are required. Specific topics discussed include IOP-lowering efficacy, adherence and persistence, preservative exposure and washout-related risk of diminished IOP reduction. Potential benefits of fixed combinations versus multiple non-fixed medications are reviewed based on a detailed literature search.EXPERT OPINION: Compared with non-fixed combinations, fixed-combination glaucoma therapies provide various demonstrated benefits (similar IOP-lowering efficacy with reduced exposure to preservatives and risk of preservative-related ocular surface disease symptoms, elimination of washout associated with insufficient time separation of instillations and reduced number of total instillations). Further, due to simplification of the instillation regimen, fixed combinations may improve treatment adherence and persistence, thereby improving stability of IOP control over time.