Peptides have a great potential for the treatment of neurological disorders, but the clinical translation is still facing significant hurdles. Delivery issues are among them: for example the short systemic half-life of peptides, poor passage across the blood brain barrier, slow diffusion through the extracellular space and rapid cerebrospinal fluid washout. This review will discuss new findings on the blood brain barrier and the physiology of the cerebrospinal fluid system, which may be relevant for the delivery of peptides to the brain. It will also discuss delivery issues and opportunities related to different administration routes, i.e. intravenous, intraventricular and intracerebral. Lastly, we summarize stem cell-based approaches; such cell therapy relies on the secretion of soluble factors, i.e. peptides. We highlight approaches to use encapsulated, genetically engineered cells as a vehicle for sustained delivery of peptides to the diseased brain.