Neurological complications are common in patients with HIV and the prevalence of neurocognitive impairment is high also among those on suppressive antiretroviral treatment (ART). Sometimes neurocognitive complications may be ascribed to CNS injury that occurred before treatment initiation (inactive disease), especially in patients with a low CD4 cell nadir; and other times to ongoing neuronal injury accompanied by chronic intrathecal immunoactivation (active disease). Cerebrospinal fluid (CSF) biomarkers of viral replication, immunoactivation, and neuronal injury provide an objective means of measuring ongoing HIV CNS infection and inflammation along with its effect on brain cells. This presentation will consider the usefulness of CSF biomarkers in measuring HIV CNS disease, particularly in HIV-infected patients on ART. Employing biomarkers for differential diagnostic purposes will also be covered. Biomarkers of CNS immunoactivation and brain injury may also be useful for research into latency and cure, and as tools for measuring the reservoir and the effect of latency-reversing agents on possible CNS immune activation and injury. However, the need to sample CSF limits the application of those measurements in a number of clinical and scientific contexts. A sensitive blood biomarker of neuronal injury continues to be sought. The resent development of a novel ultrasensitive Single Molecule Array (Simoa) immunoassay for the quantification of the neurofilament light chain protein (NFL) in blood will be presented.