Despite significant scientific progress, etiology of endometriosis remains enigmatic. New advances in molecular biology have allowed the use of proteomics in demystifying this puzzling disease. Proteomics is a technology that permits the visualization of thousands of proteins inside a cell, tissue, or organism, and simultaneous observation of any alterations in protein expression and post-translational modification that may have important, clinical implications. Owing to its capacity to reveal the structural and functional properties of proteins, proteomics might illuminate the biology of the disease much better than genomics can. This state-of-the-art technology allows us to globally compare the expression and regulation profiles of proteins found in endometriosis with normal eutopic tissues (endometrium and peritoneum), as well as to compare those found in the different forms of endometriosis (i.e., peritoneal endometriosis, endometrioma, and adenomyoma). Proteomic analysis has been employed in endometriosis research in hope of discovering endometriosis-specific proteins, pathways, and potential biomarkers for precise, early detection. In recent years, several published studies have compared serum and peritoneal fluid protein content in women with and without endometriosis, as well as protein composition in endometrial implants, eutopic endometrium, endometriomas, menstrual blood and urine. It appears that use of proteomics could revolutionize our understanding of etiopathogenesis of the disease. Some of the identified proteins could indeed be responsible for the onset and progression of endometriotic implants. Because early stages of endometriosis may be difficult to diagnose, it would be of the utmost importance to identify specific biological markers of the disease. Additionally, specific implant proteins could become targets for molecular treatment of endometriosis. It is very challenging, however, to draw clear conclusions from the analysis of the obtained samples. First of all, the samples are usually pathologically confirmed to be endometriotic, but from a molecular stand point, the particular portion of the sample that is analyzed may matter greatly; none of the methods allow us to gain information about the molecular and pathological pattern of the same sample. Secondly, it is very difficult to define an ‘unaffected peritoneum’ as a control for the endometriotic lesions. Thirdly, the variety of options in each individual makes it difficult to see the molecular picture of the diseased area (such as the ovary or peritoneum) clearly. Ideally, the samples would be of greater value if obtained at an early age, that is, before puberty in each individual and then again when endometriosis occurs later in reproductive age. Such a project cannot be performed prospectively, although it may be considered as retrospective analysis of obtained material in some patients after successful chemotherapy due to oncological conditions.