Abstract Vaccines are effective in preventing disease by stimulating the immune system and sustaining an immune response towards eradication of pathogens and diseased cells. However, designing successful vaccines is not always straightforward. For a vaccine to be successful, antigen-presenting cells (APC) need to be stimulated, primarily by adjuvants, towards a sustained immune response through integration of the innate and adaptive (humoral and cellular) immune systems. Furthermore, there is an immediate need for safe and effective adjuvants. There has been significant progress in understanding the mechanisms on how vaccines work and the role of adjuvants, dendritic cells, and the toll-like receptor (TLR) pathway. Currently, different adjuvants are actively explored but the potential of the immunoglobulin M (IgM) as a vaccine adjuvant has been overlooked. This article hypothesizes how the IgM molecule could function as a vaccine adjuvant by acting as a “soluble” toll-like receptor (TLR) through the formation of an immune complex with antigen (Ag) and other components of the innate immune system. The complex should lead to sustained humoral and/or cell-mediated immune responses. Hypothetically, it is also possible that the Ag–IgM complex recruits other components of complement or other factors that can activate other members of the adaptive immune system. As it is now possible to produce commercial-scale quantities of monoclonal human IgM antibodies, understanding the role of the IgM in linking the innate and adaptive immune systems may lead to practical therapeutic applications.