Personalized therapies play an increasingly critical role in cancer care: Image guidance with multimodality image fusion facilitates the targeting of specific tissue for tissue characterization and plays a role in drug discovery and optimization of tailored therapies. Positron-emission tomography (PET), magnetic resonance imaging (MRI), and contrast-enhanced computed tomography (CT) may offer additional information not otherwise available to the operator during minimally invasive image-guided procedures, such as biopsy and ablation. With use of multimodality image fusion for image-guided interventions, navigation with advanced modalities does not require the physical presence of the PET, MRI, or CT imaging system. Several commercially available methods of image-fusion and device navigation are reviewed along with an explanation of common tracking hardware and software. An overview of current clinical applications for multimodality navigation is provided.