The human immunodeficiency virus, HIV has long been known to be associated with CD4+ T-lymphocytopenia. In clinical practice, a low CD4 count usually implies an underlying HIV infection until proven otherwise. Non-HIV related CD4 depletion is a rare phenomenon, but has caused much public concern.A Chinese lady with unexplained CD4+ T-lymphocytopenia is presented, followed by a review of the condition as well as its practical implications. The human immunodeficiency virus, HIV has long been known to be associated with CD4 + T-lymphocytopenia. In clinical practice, a low CD4 count usually implies an underlying HIV infection until proven otherwise. Non-HIV related CD4 depletion is a rare phenomenon, but has caused much public concern. A Chinese lady with unexplained CD4 + T-lymphocytopenia is presented, followed by a review of the condition as well as its practical implications.