There is a widely held belief that the use of non-invasive imaging can reduce the gap between basic science and clinical proof-of-concept, ultimately improving decision-making and therefore the efficiency of the drug development process. Imaging techniques such as positron emission tomography (PET) and magnetic resonance imaging (MRI) are routinely used in oncology and neuroscience drug development. However, less attention has been paid to the systematic use of imaging in the cardiovascular and metabolic disease area. Here, with an emphasis on 'early clinical' development, we discuss the application of imaging in those areas, highlighting opportunities and challenges.