Despite the tremendous financial effort, the success rates of industrial drug discovery efforts continue to be unsustainably low. Academic drug discovery on the other hand provides many success stories of discovery of new medications to treat human diseases and the opening of new therapeutic paradigms to tackle previously incurable conditions. This chapter will illustrate this contribution by highlighting examples for the successful discovery of new medicines and discussing success criteria and specifics of the respective approach. Furthermore, limitations and opportunities will be discussed. Academic drug discovery can and will represent an important factor for improving current therapies, establish novel treatment concepts, and touch new territory for improving on treatment for difficult to impossible to treat human diseases, thus helping to improve the condition and extend the lifespan of many patients.