Due to absorption several ocularly applied medications give rise to systemic side-effects. The problem of systemic drug absorption should be taken into account in designing ocular drug and dosage forms so that oculospecificity of the medications is optimized. In this review we summarize the current knowledge about the systemic absorption of ocularly applied topical drugs. Special emphasis is directed to the methods that can be used to minimize systemic absorption and increase the oculospecificity of drugs, e.g., reducing volume and increasing viscosity of eyedrops, controlling drug release from depot preparations, prodrug-derivatization, and addition of vasoconstrictive agents.