Aim: To evaluate the performance of a state-of-the-art digital (dPET/CT) and long field-of-view (LAFOV) positron emission/computer tomography (PET/CT) system and to quantify how this translates into improved image quality, lesion detection, diagnostic certainty, lower dose, faster examinations and improved dynamic range. In doing so, some of the first evidence for these novel systems is provided. Methods: This thesis presents five studies which evaluate state-of-the-art dPET/CT systems by means of a matched-pair comparison of a digital with an analogue system, their performance and influence on diagnostic certainty and interrater reliability, the feasibility of reduced applied radiopharmaceutical activities in digital systems, the clinical performance of a novel LAFOV PET/CT system and the feasibility of using these for late acquisition of images for the diagnosis of recurrent prostate cancer. Results: dPET/CT systems revealed higher detection rate compared to an analogue PET/CT system as well as improved interrater reliability and diagnostic certainty. dPET/CT systems allow for 75% reduction in applied radiopharmaceutical activity or scan time. LAFOV PET/CT furnish orders of magnitude increases in count density, the possibility to reduce the total examination time to 30s or reductions in applied activity as well as the ability to examine at much later time points once multiple half-lives have elapsed without detriment to image quality. Conclusion: Digital and LAFOV PET/CT systems exhibit improved performance when compared to analogue and short-axial field-of-view systems, with demonstrated improvement in clinically relevant outcomes such as improved detection rate and diagnostic certainty.