A novel Monte Carlo (MC) technique for photon migration through 3D media with the spatially varying optical properties is presented. The employed MC technique combines the statistical weighting variance reduction and real photon paths tracing schemes. The overview of the results of applications of the developed MC technique in optical/near-infrared reflectance spectroscopy, confocal microscopy, fluorescence spectroscopy, OCT, Doppler flowmetry and Diffusing Wave Spectroscopy (DWS) are presented. In frame of the model skin represents as a complex inhomogeneous multi-layered medium, where the spatial distribution of blood and chromophores are variable within the depth. Taking into account variability of cells structure we represent the interfaces of skin layers as a quasi-random periodic wavy surfaces. The rough boundaries between the layers of different refractive indices play a significant role in the distribution of photons within the medium. The absorption properties of skin tissues in visible and NIR spectral region are estimated by taking into account the anatomical structure of skin as determined from histology, including the spatial distribution of blood vessels, water and melanin content. Model takes into account spatial distribution of fluorophores following the collagen fibers packing, whereas in epidermis and stratum corneum the distribution of fluorophores assumed to be homogeneous. Reasonable estimations for skin blood oxygen saturation and haematocrit are also included. The model is validated against analytic solution of the photon diffusion equation for semi-infinite homogeneous highly scattering medium. The results demonstrate that matching of the refractive index of the medium significantly improves the contrast and spatial resolution of the spatial photon sensitivity profile. It is also demonstrated that when model supplied with reasonable physical and structural parameters of biological tissues the results of skin reflectance spectra simulation agrees reasonably well with the results of in vivo skin spectra measurements.© (2003) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.