In research community increases the need for the search and identification of new ways in diseases diagnosis, following-up the progression of the disease, and response to the treatment. The detection technologies sensitivity improved significantly and it makes possible the quantification of detected substances in very small amounts. The tears are biological material with constantly developing possibilities in the diagnosis of different diseases. Our goal was to compile the basic overview of diagnostic potential of the tears using summary of potential tears biomarkers of different diseases. In the paper, there are described proteins biomarkers studied especially in the last years, which correlate with specific eye disease (dry eye, allergy, glaucoma, etc.). It summarizes until now published results from the range of systemic diseases in patients with scleroderma, cystic fibrosis, diabetes mellitus, multiplex sclerosis, tumors, and Parkinson’s disease as well. It focuses on proteomic analyses with the goal to specify more effectively markers, which might be used in the early diagnosis of eye diseases in the clinical practice in the future as well.