Tip-enhanced Raman Spectroscopy (TERS) has shown promise as a tool for in situ nanoscale chemical analysis, and is also leading to a better understanding of the fundamentals of surface-enhanced Raman Spectroscopy. In this work, the latest developments, challenges and applications of TERS are discussed. The focus is on tip plasmonics, single molecule detection and nanoscale chemical analysis of biological samples. (C) 2009 Elsevier B. V. All rights reserved.