Numerous compounds currently in development or recently approved have demonstrated significant and clinically relevant reduction of IOP. Differentiating factors compared with existing medications include improved side-effect profile, novel mechanisms of action, and superior reduction of IOP. Even if there are clinical advantages, however, the adoption of new medications can be uncertain due to the widespread availability of generic prostaglandin analogs. This may limit acceptance of these novel compounds as first-line agents, except for certain subgroups of glaucoma patients. Use as adjuvant or second-line therapy appears more likely for the majority of glaucoma patients.