The choroid plexus and cerebrospinal fluid have recently begun to emerge as essential regulators of neural function. Factors produced by the choroid plexus are released into the ventricular environment and thus provide a rich source of extracellular signaling molecules throughout the central nervous system. Identified factors in the cerebrospinal fluid include growth factors, hormones, proteins, peptides, lipids, glucose, microRNAs (miRNAs), messenger RNA (mRNA), and enzymes. In addition to mediating neural function, these factors have the potential to serve as biomarkers of disease states. In this review, we highlight recent advances demonstrating the importance of extracellular signaling mechanisms in mediating neural function and provide recent evidence for their role in neuropathology.