Long axial field of view (LAFOV) PET-CT scanners have been recently developed and are already in clinical use in few centers worldwide. Although still limited, the hitherto acquired experience with these novel systems highlights an increased sensitivity as their main advantage, which results in an increased lesion detectability. This attribute, alternatively, allows a reduction in PET acquisition time and/or administered radiotracer dose, while it renders delayed scanning of satisfying diagnostic accuracy possible. Another potential advantage of the new generation scanners is CT-less approaches for attenuation correction with the impact of marked reduction of radiation exposure, which may in turn lead to greater acceptance of longitudinal PET studies in the oncological setting. Further, the possibility for the first time of whole-body dynamic imaging, improved compartment modeling, and whole-body parametric imaging represent unique characteristics of the LAFOV PET-CT scanners. On the other hand, the advent of the novel LAFOV scanners is linked to specific challenges, such as the high purchase price and issues related to logistics and their optimal operation in a nuclear medicine department. Moreover, with regard to its research applications in oncology, the full potential of the new scanners can only be reached if different radiopharmaceuticals, both short and long-lived ones, as well as novel tracers, are available for use, which would, in turn, require the appropriate infrastructure in the area of radiochemistry. Although the novel LAFOV scanners are not yet widely used, this development represents an important step in the evolution of molecular imaging. This review presents the advantages and challenges of LAFOV PET-CT imaging for oncological applications with respect to static and dynamic acquisition protocols as well as to new tracers, while it provides an overview of the literature in the field.