CD4 T-cells play a crucial role in antiviral immunity and are the main targets of the HIV virus. Infection of CD4 T-cells leads to their continual depletion in the HIV infected individuals. CD4 T-cells are heterogeneous and multiple subpopulations coexist, each providing specific help to a variety of target cells (DCs, B cells, CD8 T-cells) during an immune response. CD4 T follicular helper (Tfh) cells reside in the lymph node germinal centers and are specialized in providing help to germinal center B cells. Tfh cells are a newly identified CD4 T-cell subset that has thus far been poorly characterized in humans. Their role, function and dynamics in acute and chronic viral infections are still not well defined and are currently being further explored in our laboratory. Recent studies provide initial clues that Tfh cells play a unique role in HIV infection.