Introduction <p>Success of medical therapy in glaucoma relies on a delicate yet difficult balance between efficacy, tolerability, and adherence. Preservative-free (PF) formulations enhance tolerability and adherence and, by reversing glaucoma therapy-related ocular surface disease, improve long-term efficacy and the success of medical therapy, impacting millions of patients worldwide. By increasing contact time and reducing the concentration of active ingredients gel-formulated eyedrops the aim is to optimize antiglaucoma therapy.</p> Methods <p>We review evidence for a well-established PF gel-formulated option, timolol 0.1%, and discuss the emerging potential and value of two novel PF gel-formulated agents: bimatoprost 0.01% and the fixed combination (FC) of bimatoprost 0.01%/timolol 0.1%.</p> Results <p>Cumulative evidence confirms PF gel-formulated timolol 0.1% once daily to be equivalent in efficacy to timolol 0.5% solution dosed twice daily, but safer. In a 3-month regulatory trial PF gel-formulated bimatoprost 0.01% demonstrated non-inferiority versus preserved bimatoprost 0.01% solution. More recently, a novel PF gel-formulated FC incorporated, for the first time, timolol 0.1% and bimatoprost 0.01%. By reducing the concentration of both active ingredients this FC aims to improve long-term tolerability and allow safer systemic delivery of timolol. Preliminary phase&#xa0;II controlled evidence demonstrated similar diurnal efficacy between the new FC and the popular bimatoprost 0.03%/timolol 0.5% FC. We hypothesize that the wider adoption of PF gel-formulated agents will enhance glaucoma treatment options. Finally, we identify areas of unmet need that warrant further investigation.</p> Conclusions <p>Overall, PF gel-formulated agents appear to be safer than and as effective as equivalent preserved antiglaucoma medications.</p>