Drug discovery and development is a long and arduous process and is particularly challenging for Alzheimer’s disease given the incomplete understanding of molecular mechanisms, variability in clinical presentation, relatively slow disease progression, and heterogeneous patient population. The lack of predictive preclinical models combined with the long and expensive clinical trials raise additional barriers to therapeutic development. Tens of thousands of academic publications identify potential biomarkers, molecular mechanisms, preclinical models, and interventions, yet very few have led to industry-sponsored drug development programs. In this chapter, we will describe one academic program’s approach to bridging the “valley of death.” The Stanford University SPARK Program helps academics advance their projects through the applied science stage of development, reducing the risk to potential industry partners. SPARK uses simple and easily replicated principles to ensure that more academic discoveries find their way to impact patients and to benefit society. Approximately 60% of SPARK projects advance to industry partnerships or directly into university-sponsored clinical trials.