The development of a vaccine for Lyme disease was intensely pursued in the 1990s. However, citing a lack of demand, the first human Lyme disease vaccine was withdrawn from the market less than 5 years after its approval. The public's concerns about the vaccine's safety also likely contributed to the withdrawal of the vaccine. Nearly a decade later, no vaccine for human Lyme disease exists. The expansion of Lyme disease's endemic range, as well as the difficulty of diagnosing infection and the disease's steady increase in incidence in the face of proven preventative measures, make the pursuit of a Lyme disease vaccine a worthwhile endeavor. Many believe that the negative public perception of the Lyme disease vaccine will have tarnished any future endeavors towards its development. Importantly, many of the drawbacks of the Lyme disease vaccine were apparent or foreseeable prior to its approval. These pitfalls must be confronted before the construction of a new, effective and safe human Lyme disease vaccine.