Magnetic resonance imaging is a noninvasive, volume rendering diagnostic technique that uses lanthanide complexes to enhance proton relaxation. Magnetic resonance imaging is not limited by light scattering as optical microscopic techniques are, and allows imaging of whole animals. Clinical contrast agents are nonspecific and report solely on anatomy, whereas contrast agents that can be activated can be tailored to report on the physiological status or metabolic activity of biological systems. These new classes of magnetic resonance contrast agents represent a substantial leap in the type of information that can be derived from imaging experiments, and are the focus of this review.