Since the RV144 vaccine combination showed efficacy in a Phase III trial, it provides an opportunity to generate hypotheses about the immune responses necessary for protection against HIV-1 infection, and these results could help devise vaccine candidates with higher efficacy. Here we describe how researchers can determine the correlates of immune protection for an HIV/AIDS vaccine, particularly in the context of the RV144 trial, and we discuss the terminology used to describe correlates and surrogates.