Aluminum salts (alum) have been used as components of human vaccine formulations since the early 20th century. Alum adjuvants, such as aluminum hydroxide, aluminum phosphate and aluminum hydroxyphosphate are particulate in nature, to which the vaccine antigens are adsorbed, thereby increasing antigen stability. The molecular mechanisms by which alum interacts with the human immune system continue to be studied and involve multiple pathways, both direct and indirect. Alum enhances delivery of antigen to APCs, as particulate vaccine formulations more readily interact with DCs and macrophages than soluble formulations of antigens alone. 12 Crystalline alum binds lipids on the surface of DCs and triggers a cellular activation cascade leading to initiation of an immune response, but without itself being internalized by the cells. 13 Second, alum may directly or indirectly trigger innate immunity through activation of inflammasome complexes, required for the processing of interleukin-1 family proinflammatory cytokines. This process is most likely nucleotide-binding oligomerization (NOD)-like receptor (NLR) mediated because the adjuvant effects of alum are not impaired in the absence of key Tolllike receptor (TLR)-dependent signal transduction adaptor molecules MyD88 and TRIF in knockout mice. Third, alum-induced cell death seems to modulate the local milieu in favor of enhancing adaptive immune stimulation. The release of damage-associated molecular patterns, such as uric acid and dsDNA, acts as autologously derived autoadjuvants. 14 Alum has some limitations. For instance, alum-adjuvanted vaccines often require multiple doses for induced protection4 and drive Th2-polarized over Th1-polarized immunity. At present, there are multiple licensed pediatric vaccines, such as diphtheria, tetanus and hepatitis vaccines, listing alum as essential to produce effective Ab titers. However, there are also vaccinal antigens for which addition of alum may not be necessary for effective immunogenicity. For example, alum was excluded from GlaxoSmithKline’s recent Neisseria Meningitis serogroup A, C, Y and W-135 (MenACWY) vaccine (trade name Menveo), because of the inability of alum adjuvantation to enhance serum bactericidal Ab titers in infant clinical trials. 15