Aphids are small, notorious insect pests that negatively impact plant health and agricultural productivity through direct damage, such as sap-sucking, and indirectly as vectors of plant viruses. Plants respond to aphid feeding with a variety of molecular mechanisms to mitigate damage. These responses are diverse and highly dynamic, functioning either independently or in combination. Understanding plant–aphid interactions is crucial for revealing the full range of plant defenses against aphids. When aphids infest, plants detect the damage via specific receptor proteins, initiating a signaling cascade that activates defense mechanisms. These defenses include a complex interaction of phytohormones that trigger defense pathways, secondary metabolites that deter aphid feeding and reproduction, lectins and protease inhibitors that disrupt aphid physiology, and elicitors that activate further defense responses. Meanwhile, aphids counteract plant defenses with salivary effectors and proteins that suppress plant defenses, aiding in their successful colonization. This review offers a detailed overview of the molecular mechanisms involved in plant–aphid interactions, emphasizing both established and emerging plant defense strategies. Its uniqueness lies in synthesizing the recent progress made in plant defense responses to aphids, along with aphids’ countermeasures to evade such defenses. By consolidating current knowledge, this review provides key insights for developing sustainable strategies to achieve crop protection and minimize dependence on chemical pesticides.