A challenge in cancer therapy is to selectively target activities that are essential for survival of malignant cells while sparing normal cells. Translational control represents a potential anti-neoplastic target because it is exerted by major signaling pathways that are often usurped in cancers. Herein we describe approaches being developed that target eukaryotic initiation factor (eIF) 4F, a heterotrimeric complex that integrates multiple signaling inputs to the translation apparatus.