Long-term non-progressors (LTNP) are human immunodeficiency virus (HIV)-infected individuals characterized by the absence of disease, low viral loads and stable or even increasing CD4(+) T cell counts for prolonged periods of time. In these subjects, an HIV-specific immune response which is either stronger or directed against a wider array of viral epitopes than that seen in progressors, can be often detected. Here, we summarize the characteristics of HIV-specific CD4(+) and CD8(+) T cell responses in LTNP, and discuss how a highly effective T cell-mediated immune response against HIV might contribute to the establishment of this particular condition.