Dry eye disease (DED) is a multifactorial disease of the ocular surface that may be accompanied by discomfort and visual disturbances to a level that reduces quality of life. Artificial tears are a common first-line therapy for DED that aim to supplement the tear film but do not address the underlying causes of DED. Because of the complexity and variability of the disease, personalized treatment beyond artificial tears is important for successful management. This review describes artificial tears and the current knowledge in the personalized approach to the management of DED. There is evidence that artificial tears can reduce symptoms and signs of DED; however, a proportion of patients have been found to show limited or no improvement with artificial tears. Furthermore, the effectiveness of artificial tears may depend on patient compliance and type of artificial tear product used. Personalized management of DED with other treatments involves identifying features of the disease, including the subtype of DED, the presence of inflammation, and the coexistence of external and behavioral contributing factors. Various measures exist to characterize DED, including assessments of the tear film lipid layer, the meibomian glands, tear volume, tear osmolarity, and matrix metalloproteinase 9 levels. Because individuals can show variable features, the most prominent clinical findings, comorbidities, triggering events, and treatment history should be considered to determine the best treatment choices for patients.