This talk will highlight the mechanisms that control nuclear export of proteins, focusing on the XPO1 and Msn5 export pathways. XPO1 recognizes classical nuclear export signals (NESs) in protein cargoes and has become an important therapeutic target in cancer treatment. The XPO1 inhibitor selinexor was approved for multiple myeloma in 2019, yet ongoing studies continue to reveal unexpected modes of action that provide new insights into XPO1 biology. The presentation will also examine Msn5, an exportin that transports dozens of proteins from the nucleus by recognizing phosphorylation-dependent NESs that are structurally and mechanistically distinct from the classical NESs recognized by XPO1. These studies illustrate both the diversity of nuclear export pathways and opportunities for therapeutic intervention.