Sampling of cerebrospinal fluid (CSF) is an essential step for early-phase drug development studies, and particularly for studies in neurology. As CSF drug concentrations reflect unbound drug concentrations in the brain, this procedure is of critical importance for gaining insight into the delivery of drugs that act on targets in the central nervous system (CNS). In addition, CSF biomarkers are vital for indicating pharmacodynamic action of CNS drugs in clinical trials, as well as providing an excellent basis for go/no go decisions in the drug development process.