Surface-enhanced Raman scattering (SERS) permits multidisciplinary trace analyses and the potential detection of single molecules. Shi Bai and Koji Sugioka from RIKEN report a comprehensive review of recent progress in strategies for the fabrication of highly sensitive SERS substrates. Femtosecond laser-based techniques are discussed as a versatile tool for the fabrication of SERS substrates. Several approaches are highlighted for enhancing the performance of SERS sensing devices, and real-time sensing and biological applications are reviewed.