There is growing interest in the role of anti-HIV antibody-dependent cellular cytotoxicity (ADCC) antibodies in the prevention and control of HIV infection. Passive transfer studies in macaques support a role for the Fc region of antibodies in assisting in the prevention of simian-human immunodeficiency virus (SHIV) infection. The Thai RV144 HIV-1 vaccine trial induced anti-HIV ADCC antibodies that may have played a role in the partial protection observed. Several observational studies support a role for ADCC antibodies in slowing HIV disease progression. However, HIV evolves to escape ADCC antibodies and chronic HIV infections causes dysfunction of effector cells such as natural killer (NK) cells that mediate the ADCC functions. Further, four recent studies show that the HIV-1 Vpu protein, by promoting release of virions, reduces the capacity of ADCC antibodies to recognize HIV-infected cells. The review dissects some of the recent research on HIV-specific ADCC antibodies and discusses mechanisms to further harness ADCC antibodies in the prevention and control of HIV infection.