Non-specific targets such as DNA and microtubules have been the mainstay of cancer therapeutics and the most effective clinical agents until a decade ago. Advances in genetics, molecular and cellular biology over the past decade led to the development of a new generation of agents that are far more specific and effective. In contrast to progress seen with therapeutic agents, general monitoring targets such as proliferation imaging are just gaining momentum and targeted imaging is still in its infancy. In these paradoxical times, this review assesses the role of proliferation imaging in monitoring the efficacy of targeted therapeutics.