Medical images represent maps of the spatial distribution of tissue properties. Each modality probes a specific set of tissue properties such as x-ray attenuation for computed tomography, transmission of sound for ultrasound, and the rate of glucose uptake for fluorodeoxyglucose-positron emission tomography. Understanding the basic principal underlying each modality is important for developing approaches to utilize imaging in cancer research and clinical care. In addition, each modality has specific challenges related to reliable quantitation that are important to appreciate.