Various new topical ophthalmic drug delivery systems show promise for increasing bioavailability, reducing epithelial toxicity, and improving patient compliance. Microparticulates are drug-containing polymeric particles that are placed in the fornix and release ocular medication by diffusion, chemical reaction, polymer degradation, or ion exchange and can be used to deliver many topical ophthalmic medications, including antibiotics and antimetabolites. Soft drugs are activated enzymatically at the site of application and are rapidly converted to inactive metabolites when exposed to the ocular environment, improving bioavailability at the target site, and reducing the potential for ocular and systemic side effects. Applications include soft beta-blockers, soft corticosteroids, and soft anticholinergics. Collasomes are made up of collagen pieces suspended in a viscous vehicle; this formulation is similar to that of corneal collagen shields, but is more useful for chronic therapy because the collasomes can be instilled by the patient and cause less blurring of vision. Potential uses include delivery of hydrophobic antimetabolites such as cyclosporine to prevent graft rejection and delivery of lipids for the therapy of dry eyes. Ideal replacements for dysfunctional tear layers, especially the lipid layer, have not yet been developed. The toxic effects of preservatives in topical ocular medications, particularly in artificial tears, often outweigh the benefits and preservative-free tear preparations are almost always preferable.