The dual variable domain immunoglobulin (DVD-Ig™) protein is a new type of dual-specific IgG. As a novel therapeutic class, the great potential of the DVD-Ig protein is to simultaneously target two mediators of disease by a single pharmaceutical entity. The molecule contains an Fc region and constant regions in a configuration similar to a conventional IgG; however, the DVD-Ig protein is unique in that each arm of the molecule contains two variable domains (VDs). The VDs within an arm are linked in tandem and can possess different binding specificities. Here, we discuss critical design features of the DVD-Ig protein and describe a methodology for cloning, expressing, and purifying the molecules.