Computed tomography (CT), a cornerstone of medical imaging, has undergone dramatic transformations with the advent of spectral photon-counting computed tomography (SPCCT), which addresses some limitations of traditional CT systems. This chapter focuses on recent advances in contrast agents tailored for SPCCT and their clinical potential. The chapter explores the following three themes related to SPCCT contrast agents: (1) utilizing currently approved contrast agents and exploring new combinations thereof, (2) developing new contrast agents based on nanoparticles (NP), and (3) employing novel agents for tracking cells and materials such as hydrogels. This exploration includes a detailed analysis of their applications, accompanied by a careful examination of safety and biocompatibility. The chapter concludes by emphasizing the crucial importance of safety considerations in SPCCT contrast agent design and addressing the challenges that remain in their optimization, including parameter balancing and injection protocols.