Although many new prevention modalities that include the use of antiretroviral drugs show promise, there is no question that a global solution to the HIV epidemic will not be economically or logistically feasible without the development of vaccine that provides durable protection. In the best case scenario, the vaccine has to protect against acquisition of infection, likely mediated by Env-specific B-cell responses combined with CD4+ T-cell responses to evoke full maturation and maintenance of protective antibodies. But HIV-specific CD8+ T-cell responses are also likely to be a key element, particularly for those inevitable situations in which full vaccine-induced protection from acquisition is not achieved, in which case durable control of established infection will be required. Although there is reason to be optimistic that an effective HIV vaccine is possible, one of the major constraints moving forward will likely be constraint on funding to support a diversity of concepts at a time that the correlates of protection from acquisition and disease progression are still unknown. Given the scope of the epidemic and the economic climate, we must strive to do much more with less and seek to access additional resources, both scientific and monetary, from every possible source.