Peripheral neuropathy is responsible for significant disability worldwide. However, a comprehensive diagnostic evaluation of this condition is cumbersome and costly. A structured clinical approach is necessary for efficient localization and characterization of neuropathy and targeted diagnostic testing. In this clinical article, Olajide Williams MD, Assistant Professor of Neurology at Columbia University, explains the important elements of the clinical history and physical examination and the use of electrodiagnosis and quantitative sensory testing, including skin, nerve, and muscle biopsy. A new proposed criterion for the diagnosis of small fiber neuropathy is discussed and an updated list of neuropathy provoking drugs has been included.