The complexity of vaccines creates a unique formulation challenge. Vaccines may consist of one or more types of antigenic component including live attenuated or killed viral or bacterial particles, polysaccharides, proteins, polynucleotides and particle conjugates. In addition, other excipients such as adjuvants may be present. Not only must the chemical and structural integrity of the various components be maintained, but immunogenicity must be ensured. The inherent lability of vaccines can critically limit their distribution, administration, and efficacy in parts of world where it is difficult to maintain a cold chain. Combination with other vaccines and oral administration may also compromise vaccine stability. Successful vaccine stabilization strategies include both empirical efforts to screen and identify appropriate stabilizers and environmental conditions and more rational approaches toward developing an understanding of the causes and mechanisms of vaccine inactivation. In principle, by elucidating the conformational and chemical pathways of macromolecular inactivation, more rational strategies to minimize their occurrence can be adopted. This presentation will review the application of classical techniques such as viral plaque assays to identify vaccine stabilizers by empirical testing. The potential of using various biophysical techniques (both hydrodynamic and spectroscopic methods) to characterize the physicochemical stability of purified vaccine preparations (Hepatitis A and B) is also explored.