This chapter presents the case of a 57-year-old right-handed man with a 1-year history of poor balance, increasing forgetfulness, and difficulties following conversations. There is a family history of malignancy in two first-degree relatives. Neurological examination reveals saccadic pursuit eye movements but no nystagmus, impaired fine finger movements, depressed ankle jerks, and impaired vibration and temperature sensation in both distal lower limbs. HIV associated neurocognitive disorder (HAND) varies in severity from the asymptomatically neurocognitively impaired to those with dementia. Risk factors for the development of HIV dementia (HAD) include: persistently high viral load, low nadir CD4 cell count, increasing age and female sex, low body mass index, anaemia, and intravenous drug abuse. HAND varies in severity from the asymptomatically neurocognitively impaired to those with dementia. The CNS damage underlying HAND occurs secondarily to the direct toxic action of virus-produced proteins and as a consequence of immune activation.