Two different strategies have been developed for imaging the proliferative status of solid tumors with the functional imaging technique, Positron Emission Tomography (PET). The first strategy uses carbon-11 labeled thymidine and/or, more recently, fluorine-18 labeled thymidine analogs. These agents are a substrate for the enzyme thymidine kinase-1 (TK-1) and provide a pulse label of the number of cells in S phase. The second method for imaging the proliferative status of a tumor uses radiolabeled ligands that bind to the sigma-2 receptor which has a 10-fold higher density in proliferating (P) tumor cells versus quiescent (Q) tumor cells. This article compares and contrasts the two different strategies for imaging the proliferative status of solid tumors, and describes the strengths and weaknesses of each approach.