The history and development of 25-gauge transconjunctival sutureless vitrectomy are reviewed in this paper. The expanded spectrum of appropriate cases and recent innovations in vitrectomy surgery are discussed, as are longer-term outcomes and possible complications. 25-Gauge pars plana vitrectomy has evolved significantly since its introduction in 2002, with newer instruments and novel techniques expanding the scope and improving outcomes in vitreoretinal surgery. Proper case selection is imperative, as the smaller scale of the instruments and decreased fluidics work most efficiently when extensive manipulation of intraocular tissue or significant membrane dissection is not required. Unique complications of 25-gauge surgery such as hypotony and a possible increased rate of endophthalmitis may be related to unsutured sclerotomies, and revisions in surgical approach may help to decrease these potentially devastating complications. Clinical experience over the last several years has proven that this sutureless system is both safe and efficacious. Decreased surgical times, reduced postoperative inflammation, and more rapid patient recovery have all contributed to an increased acceptance of 25-gauge vitrectomy by retinal physicians.