An innovative spectroscopic technique to determine the drug concentration in biological fluids is discussed. We introduce the context of drugs with narrow therapeutic index in relation to epilepsy and Parkinson’s disease. We then recapitulate the essentials of Raman and enhanced Raman spectroscopy that makes use of a corrugated metallic surface. Optimizing the intensification of the spectroscopic signatures of a given analyte critically depends on the metal choice and on the fine details of the induced surface nanostructuring. We review the topic with emphasis on noble metal surfaces synthesized by pulsed laser ablation in inert gas at high pressure. The performance of optimized surfaces to determine the drug concentration in different fluids, including human blood, is discussed with reference to carbamazepine, an anti-epileptic drug widely adopted in Developing Countries and to apomorphine, a drug used to treat via subcutaneous injection patients with important manifestations of Parkinson’s disease.