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In contrast to other interstitial applications of photodynamic therapy (PDT), optical guidance or monitoring in the head and neck is at a very early stage of development. The present paper reviews the use of optical approaches, in particular optical spectroscopy, that have been used or have the potential to guide the application of PDT. When considering the usefulness of these methods, it is important to consider the volume over which these measurements are acquired, the influence of differences in and changes to the background optical properties, the implications for these effects on the measured parameters and the difficulty of incorporating these types of measurements in clinical practice in head and neck PDT. To illustrate these considerations, we present an application of a recently developed technique, which we term fluorescence differential path length spectroscopy for monitoring meta-tetra(hydroxyphenyl)-chlorin or Foscan-PDT of interstitial head and neck cancer.