Receptor internalization is a critical step in the cellular uptake of antibody-conjugated drugs, and defects in this pathway pose a potential avenue for drug resistance in some cancers. The cover depicts fluorescence microscopy showing phosphorylated Caveolin-1 (pCAV1, red) with the growth factor receptor HER2, labeled here with the anti-HER2 antibody trastuzumab (green; DAPI-labeled nuclei shown in blue). Yellow regions represent areas where HER2 and pCAV1 colocalize, leading to internalization of the trastuzumab-bound HER2 protein. In this issue, Indira Chandran and colleagues demonstrate that hypoxic conditions redistribute pCAV1 and its association with HER2, thereby inhibiting HER2 internalization and, by extension, uptake of trastuzumab-conjugated chemotherapeutics. For more information, see the Highlight on page 515 and the article on page 644.