The relative non-specificity of the first generation MR contrast agents has meant that a new approach to their design is required. This review focuses on a new class of more specific or functional agents. These are the so-called “activated”, “smart” or “responsive” contrast agents. The relaxivity of an activated contrast agent is responsive to (or can be modulated by) a particular in vivo stimulus such as a change in biological environment or activity. More specifically, a “switching on” of contrast in response to an event such as a change in physiological pH, metal ion concentration, enzyme activity or partial pressure of oxygen is sought. The current generation of activated MR contrast agents is discussed herein.