Systems and methods for image guidance, which may include an image processing unit, cameras, and handheld real-time imaging components or handheld displays, wherein the cameras observe visual features on patients, tools, or other components, and wherein said features allow camera or object positions to be determined relative to secondary image data or a reference position, and wherein the image processing unit is configured to dynamically register observations with secondary image data, and to compute enhanced images based on combinations of one or more of secondary image data, positioning data, and real-time imaging data.