Despite being developed over 30 years ago, 2-deoxy-2-[(18)F]fluoro-D-glucose remains the most frequently used radiotracer in PET oncology. In the last decade, interest in new and more specific radiotracers for imaging biological processes of oncologic interest has increased exponentially. This review summarizes the strategies underlying the development of those probes together with their validation and status of clinical translation; a brief summary of new radiochemistry strategies applicable to PET imaging is also included. The article finishes with a consideration of the challenges imaging scientists must overcome to bring about increased adoption of PET as a diagnostic or pharmacologic tool.