Methods and compositions for use in treating anxiety are provided. In the subject methods, an effective amount of an agent having ApoE3 activity is administered to a host suffering from an anxiety, e.g. excessive anxiety, unwanted anxiety, an anxiety disorder, etc. Also provided are methods and compositions for modulating adrenal steroidogenesis and/or release, particularly stress induced adrenal steroidogenesis and/or release, and the hippocampal-pituitary-adrenal (HPA) axis. In these methods, an effective amount of an ApoE activity modulating agent, e.g. an ApoE agonist or antagonist, is administered to the host.