The omega-3 (ω3) and omega-6 (ω6) essential fatty acid knowledge base has been exploding. In the last 5 years, at least 12 clinical trials on ω3 and ω6 supplementation and dry eye disease (DED) were published in the peer-reviewed literature (2010 to 2015), about double the amount published in the 5 years prior. Although there is increasing scientific evidence that supports the potential use of ω3 and ω6 supplementation for DED, there are limited randomized controlled trials to properly inform evidence-based medicine. Dry eye disease is one of the most common eye conditions that patients seek care for and cannot be disregarded as a trivial condition. The roles of ω3 and ω6 polyunsaturated fatty acids (PUFAs) in the treatment of DED are still not completely understood. There are distinct and sometimes opposite effects of ω3 and ω6 PUFAs, both of which are essential and cannot be synthesized de novo in the body. These fatty acids must be obtained from the diet, which varies widely by region, even within the United States. Omega-3 PUFAs have anti-inflammatory effects; a proper ratio of ω6:ω3 in the diet must be established. Objectively correlating changes in dry eye syndrome with blood levels of ω3 PUFAs has not been done in a large-scale multisite study. Just as Wilder's law of initial value states that "the direction of response of a body function to any agent depends to a large degree on the initial level of that function," the baseline status needs to be taken into account. There is also no consensus on the dose, composition, length of treatment, and so on with ω3 or ω6 PUFAs. Increased quality evidence on the usefulness of over-the-counter supplements is needed to enable eye care providers to confidently outline specific treatment recommendations for using ω3 PUFAs in DED.