Abstract: Drug transporters mediate different types of drugs with diverse structures across cell membranes, affecting concentration of drugs in various tissues and organs and the systemic exposure. They are not only key factors that determine drug efficacy, but also important sites for drug-drug interaction. The major human drug transporters belong to the ATP-binding cassette (ABC) superfamily or the solute carrier superfamily, which mediate the efflux and absorption of drugs, respectively. These two kinds of transporters coordinate with each other and work in concert to determine intracellular drug concentrations. As membrane proteins, drug transporters need to go through a series of precise and complicated post-translational modifications before arriving at the site of action. Additionally, the human body needs to respond promptly during the intake of drugs and post-translational regulations hence become the manner of choice in such a process; The function of transporters may be affected by the abnormality of various post-translational regulatory mechanisms under pathological conditions as well. Therefore, a comprehensive understanding of the post-translational processing of drug transporters is of great importance for investigating the molecular mechanism(s) of drug transport and clarifying the inter-individual variability of drug response caused by genetic polymorphisms. The present article reviewed current reports on post-translational processing and modification of drug transporters, and summarized essential motifs and/or sites in transporters that play key roles in these regulatory processes.