Despite the fact that different administration routes and delivery systems have been used for interleukin-2 (IL-2) delivery, little has been reported regarding the most efficient strategies used to deliver IL-2 in a nontoxic, efficient, stable and safe manner. Systemic IL-2 administration has always been associated with rapid clearance and severe toxicity as a result of its narrow therapeutic index. Loco-regional IL-2 delivery, however, is used to localize IL-2 actions and activities into the vicinity of tumors and can result in an improved therapeutic outcome with much less side effects or toxicity. The purpose of this review is to report on the different properties and aspects of IL-2, including its mechanism of action, physicochemical properties, and structure which have an impact on the activity, stability and formulation of IL-2 dosage forms and delivery systems. In addition, advantages and limitations of the currently available techniques and strategies to deliver IL-2 will also be covered.