Accurate intra-body navigation is used in various surgical and diagnostic procedures. In cardiac ablation procedures catheters are inserted into the heart through various blood vessels and are used for mapping the mechanical geometry and electrical activity of the heart, and also for ablation aimed at stopping arrhythmias. In the lungs, electromagnetic navigation is used for getting the biopsy tools to the lesions while navigating through the bronchial airway tree. Accurate navigation within the human body presents a set of challenging technological and mathematical problems. In this talk I will cover the principles of the intra-body navigation and the main mathematical challenges which have to be overcome in order to make the navigation accurate and useful.