To date, symptomatic medications prevail as the mainstay of treatment options for Alzheimer's disease (AD). There have been tremendous investments made to increase the numbers of drugs approved and the targets engaged, in an effort to alter the disease course or pathophysiology of AD. Unfortunately, almost all studies have not met expectations and no new drug (beyond medical foods) has been approved for the treatment of AD in the last decade. This review is a comparison of novel AD therapies in the late phases of clinical testing, including recent high-profile clinical failures, and agents in development with relatively unexplored mechanisms of action, with a focus on their potential as therapeutic agents and their proposed advantages over the treatments currently in use.