Biological luminescence stimulated by optical excitation results in signals which are characteristic of the host tissue. The spectrum of the emitted light, the intensity, and the excited state lifetimes are modified as the result of disease or by activation through addition of cell selective phosphors. There is an opportunity to identify diseased tissue both by the spectral signals from activators or, in some cases, by the differences of the natural luminescence responses. For practical reasons, defined by the sensitivity range of standard luminescence detectors, much of the current work has focussed on the short wavelength emissions driven by laser activation. However, the techniques are poised to undergo a dramatic expansion in scope with the advent of higher sensitivity photocathodes with high efficiency responses at long wavelengths. It is now possible to utilise a greater range of emission features with improved discrimination. Further, movement to longer wavelength excitation, and emission, open the way to probe deeper beneath the surface of tissue. The current overview will focus on recent examples from detection of cancer to tooth caries and indicate how the non-destructive luminescence probes can distinguish between tissue changes at an early stage of development.