In ocular tissue, arachidonic acid is metabolized by cyclooxygenase to prostaglandins which are the most important lipid derived mediators of inflammation. Presently nonsteroidal anti-inflammatory drugs (NSAIDs) which are cyclooxygenase (COX) inhibitors are being used for the treatment of inflammatory disorders. NSAIDs used in ophthalmology, topically, are salicylic-, indole acetic-, aryl acetic-, aryl propionic- and enolic acid derivatives. NSAIDs are weak acids with pKa mostly between 3.5 and 4.5, and are poorly soluble in water. Aqueous ophthalmic solutions of NSAIDs have been made using sodium, potassium, tromethamine and lysine salts or complexing with cyclodextrins/solubilizer. Ocular penetration of NSAID demands an acidic ophthalmic solution where cyclodextrin could prevent precipitation of drug and minimize its ocular irritation potential. The incompatibility of NSAID with benzalkonium chloride is avoided by using polysorbate 80, cyclodextrins or tromethamine. Lysine salts and alpha-tocopheryl polyethylene glycol succinate disrupt corneal integrity, and their use requires caution. Thus a nonirritating ophthalmic solution of NSAID could be formulated by dissolving an appropriate water-soluble salt, in the presence of cyclodextrin or tromethamine (if needed) in mildly acidified purified water (if stability permits) with or without benzalkonium chloride and polyvinyl alcohol. Amide prodrugs met with mixed success due to incomplete intraocular hydrolysis. Suspension and ocular inserts appear irritating to the inflamed eye. Oil drop may be a suitable option for insoluble drugs and ointment may be used for sustained effect. Recent studies showed that the use of colloidal nanoparticle formulations and the potent COX 2 inhibitor bromfenac may enhance NSAID efficacy in eye preparations.