The dry eye disease (DED) is a chronic multifactorial disorder of the tears that also involves the ocular surface, the lacrimal glands, and meibomian dysfunction. Furthermore, DED is often associated with Sjögren's syndrome (SS) and other autoimmune disorders. Sometimes, this chronic or subclinical condition is difficult to diagnose and treat, due to its heterogeneity. Areas covered: A literature search of relevant publications about treatment of DED was performed. All relevant articles published between 2011 and 2016 were identified through a computerized search for reviews and clinical trials using the Pub Med database. In particular, investigational treatments have been reported in this peer-reviewed publication. Relevant articles identified were manually searched and reviewed, then data concerning with novel treatment for DED were included into the manuscript. Expert opinion: The treatment of dry eye patients evolves continuously because DED seriously impacts the quality of life of older adults. Indeed, as a chronic disease, DED prevalence is expected to worsen with the aging population. For this reason, current efforts focus on combined pharmacological strategies targeted towards multiple systems. Probably this is the correct way to reach a long lasting symptoms relief treatment that may allow an actual improvement of patients' quality of life.