Dry eye disease (DED) is a highly prevalent chronic ocular disorder that can lead to significant discomfort and visual disturbance. It is a potentially debilitating condition that can have significant negative impact on quality of life. A diverse range of management options exists for DED, including tear supplement products, anti-inflammatory agents, immunomodulators, punctal occlusive devices, and environmental modifiers. Although the availability of a variety of treatment approaches provides clinical flexibility and can enable individualized care, it can also complicate clinical management decisions and lead to variability in the nature of the clinical care provided to patients. By considering two dry eye case scenarios, this review evaluates the currently available evidence relating to DED therapy to describe a pragmatic clinical approach to best-practice management of dry eye patients.