Pharmacologic vitreolysis with ocriplasmin has emerged as a new option for the treatment of symptomatic vitreomacular traction syndrome (VMT). Not all cases of VMT require therapy. Knowledge of the natural history of VMT is essential for patient counselling and for deciding between observation and treatment. Ocriplasmin treatment for VMT may provide very good results if used with the correct candidates. On the other hand, observation might be the best option in cases of VMT with high chances of spontaneous resolution. The purpose of this review is to report on the natural course of VMT based on the current literature, present briefly the author’s experience with the use of ocriplasmin in cases of VMT, and provide practical hints for the implementation of this treatment modality in the clinical setting.