In the past several decades, a number of novel fluorescence image-guided surgery (FGS) contrast agents have been under development, with many in clinical translation and undergoing clinical trials. In this review, we have identified and summarized the contrast agents currently undergoing clinical translation. In total, 39 novel FGS contrast agents are being studied in 85 clinical trials. Four FGS contrast agents are currently being studied in phase III clinical trials and are poised to reach FDA approval within the next two to three years. Among all novel FGS contrast agents, a wide variety of probe types, targeting mechanisms, and fluorescence properties exists. Clinically available FGS imaging systems have been developed for FDA approved FGS contrast agents, and thus further clinical development is required to yield FGS imaging systems tuned for the variety of contrast agents in the clinical pipeline. Additionally, study of current FGS contrast agents for additional disease types and development of anatomy specific contrast agents is required to provide surgeons FGS tools for all surgical specialties and aßociated comorbidities. The work reviewed here represents a significant effort from many groups and further development of this promising technology will have an enormous impact on surgical outcomes acroß all specialties.