Although perfluorochemicals (PFCs) are known for their ability to carry oxygen, they are the most versatile and only universal contrast agents with important applications using x-ray, ultrasound, or magnetic resonance (MR). The characteristics that make them unique diagnostic agents are lack of hydrogen atoms, immiscibility with water, low surface tension, compressibility, and long intravascular persistence when emulsified and given i.v. When made radiopaque, they are visible with x-ray computed tomography (CT) and standard radiography. Because the neat liquid is inert it can be ingested, instilled in the lung, or introduced into any hollow organ to image the lumen without untoward effects. The long intravascular persistence allows the imaging of blood vessels and vascularized tissues. Small or deep vessels become visible on Color Doppler Imaging and angiographic images of any vascular tree including the coronaries can be rendered from the serial CT images. As PFCs accumulate within RE cells, specific liver and spleen enhancement is achieved allowing the detection of small tumors within these organs. When injected interstitially, the particles find their way to the draining lymphnodes providing detail of the internal architecture to detect the presence or absence of tumor involvement on both CT and sonography. Using 19F MR, tissue perfusion and tissue pO2 measurements can be achieved. As can be seen, the applications of PFC in diagnosis are vast, unique, and important. These new capabilities will carry radiological tools to new horizons.