Molecular imaging is nowadays gaining a complementary role in cancer therapy, specifically in diagnosis, selection of therapy, monitoring of therapeutic efficacy, and also in the surgical setting. Many tumor-targeted tracers have been developed for these applications. Optical molecular imaging has been gaining more importance, particularly due to the absence of ionizing radiation, rendering its use friendlier and safer for patients and medical personnel. Recently, clinical trials have been initiated for tumor optical imaging with monoclonal antibodies conjugated to the near-infrared fluorophore IRDye 800CW. Yet, preclinical studies clearly indicate several aspects that favor smaller tracer formats over antibodies, namely, their rapid distribution, efficient penetration, and the rapid clearance of unbound tracers. Altogether, these small tracers lead to adequate contrast within minutes or hours after administration, instead of days. Here, the discussion will be centered on the properties of the different formats of tracers, in particular the small formats. Although, the conventional antibody format has already reached clinical trials, optical imaging trials with smaller formats are eagerly awaited to clarify whether their advantages over antibodies are also evident in patients.