The treatment of genetic diseases using therapeutic gene transfer is considered to be a significant development. This development has brought with it certain limitations, and the process of overcoming these barriers has seen a drastic change in gene delivery. Many metal ions such as Mg2+, Mn2+, Ba2+ and, most importantly, Ca2+ have been demonstrated to have significant roles in gene delivery. Recently, calcium phosphate alone, or in combination with viral and nonviral vectors, was found to exert a positive effect on gene transfer when incorporated in the colloidal particulate system, which is an advancing approach to gene delivery. This review elaborates on various successful methods of using calcium in gene delivery.