Recently, it has become evident that pharmaceutical excipients may interfere with the activity of ATP-binding cassette (ABC) transporters and solute carriers (SLC). The present review aims to provide an overview of surfactants shown to modulate substrate transport via SLCs and ABCs, and to discuss the relevance for oral drug absorption. In vitro, more than hundred surfactants have been suggested to decrease the efflux activity of P-glycoprotein (P-gp, ABCB1), and many of these surfactants also inhibit the breast cancer resistance protein (BCPR, ABCG2), while conflicting results have been reported for multidrug resistance-associated protein 2 (MRP2, ABCC2). In animals, surfactants such as pluronic® P85 and polysorbate 20 have been shown to enhance the oral absorption of P-gp and BCRP substrates. Many surfactants, including cremophor® EL and Solutol® HS 15 inhibiting ABC transporters, were also found to inhibit SLCs in cell cultures. These carriers were SLC16A1, SLC21A3, SLC21A9, SLC15A1-2, and SLC22A1-3. This overlap in specificity of surfactants that inhibit both transporters and carriers might influence the oral absorption of various drug substances, nutrients, and vitamins. Such biopharmaceutical elements may be relevant for future drug formulation design.