The Monte Carlo simulation of particle transport and interaction in matter finds growing applications in medical radiation physics. Dosimetric applications in radiation therapy span from internal dosimetry in radionuclide therapy of nuclear medicine, to the treatment planning in external beam radiation therapy with photons, electrons or fast heavy ions, to the assessment of radiation dose distribution in heterogeneous media such as lungs, bones or renal parenchyma.After a general introduction on the different Monte Carlo packages available (Geant4, Fluka, EGS, MCNP, etc.), we focus on the validation of physical models and parametrizations mostly relevant in the energy range of interest for medical applications, and on the comparison of the outcomes from the various simulation packages.We then report on the recent applications of such packages in the development of new and more accurate models for external beam radiation therapy with photons and electrons, hadron therapy applications, and the internal dosimetry of radionuclides in nuclear medicine treatments. A perspective on the new results in the field of sub-millimeter scale internal dosimetry of tissue and vascular structures will be given, together with a review of the studies on cellular microdosimetry. © 2013 by Nova Science Publishers, Inc. All rights reserved.