Infection with the human immunodeficiency virus (HIV-1) results in a severe immunodeficiency characterized by a depletion of CD4+ T-helper cells. Furthermore it is well documented that in asymptomatic persons the number of CD4+ cells is also a good predictor of progression to AIDS. However, persons with similar CD4+ cell counts may differ with regard to clinical progression. For this reason the development of additional markers predictive of disease progression is of major clinical importance. In this review three additional progression markers are discussed: rate of decline of CD4+ cells, T-cell reactivity and HIV biological phenotype. Besides their usefulness as independent progression markers they also provide insight into the immunopathological mechanisms responsible for the final development of AIDS.