Since about 20 years, the large panel of the antiglaucoma eyedrops has drastically changed the management of glaucoma. Indications for filtering surgery had decreased in frequency. A great number of patients are controlled only by medications. However ocular intolerance and side effects have been reported until in 50% of the cases with 10% of severe manifestations of intolerance. Ocular side effects to topical medications may very often alter compliance. Ocular intolerance had been shown to be secondary to immunological mechanisms and direct or indirect toxicity. The immunological or allergic mechanisms are induced by a type I or IV hypersensibility and only represent 3% to 10% of all the side effects induced by topical medications. Toxic effect can be a direct through different mechanisms: pure toxic effect, acid pH, osmolarity of the solution, photosensibilisation. This will induce inflammatory reaction that will produce fibrosis in the long term. This toxic effect can be worsened by eye dryness or rosacea. Toxicity can also be indirect through an alteration of the conjunctival microbial flora and/or the lacrymal secretion. Concomitant obstruction of the lacrymal ducts may also contribute to this effect. These mechanisms could have been elucidated thank to histological studies from conjunctival mark, and more recently with confocal HRT, which gives an analysis of the ocular surface in vivo. Appropriate and early detection of intolerance to antiglaucoma medications is mandatory to adjust management strategies accordingly. These are based on the suppression or the reduction of conservative agents whenever possible, the use of fixed combinations, the reduction of the number of the instillations and the associated treatment of the ocular surface.