Major advances in the field of carrier-mediated agents (CMAs) have revolutionized drug delivery capabilities over the past decade. While providing numerous advantages over their small-molecule counterparts (solubility,duration of exposure, and delivery to the site of action are higher), these agents display substantial variability in systemic clearance (CL) and distribution, tumor delivery, and pharmacologic effects. This review provides an overview of factors that affect the pharmacokinetics (PK) and pharmacodynamics (PD) of CMAs in preclinical models and patients.