Zeta potential is a scientific term for electrokinetic potential in colloidal systems which has a major effect on the various properties of nano-drug delivery systems. Presently, colloidal nano-carriers are growing at a remarkable rate owing to their strong potential for overcoming old challenges such as poor drug solubility and bioavailability. Furthermore, they show an unlimited capacity in the field of drug targeting. The properties of nano-medicines such as release from dosage forms at specific sites as well as drug circulation and absorption into body membranes are dramatically affected by some physical and chemical characteristics of nano-drugs. Particle size and charge are two major factors which could play key roles in this regard. In this paper, the effect of zeta potential on different properties of nano-drug delivery systems is reviewed.