Many proteins have “neurotrophic” activities in in vitro or in vivo test systems. Originally these were discovered as certain neurotrophic activities with unknown molecular structures. Nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), and ciliary neurotrophic factor (CNTF) were discovered by their specific neurotrophic properties. They were purified from tissue extracts using in vitro bioassays based on the survival of specific nerve cells and subsequently all or part of their primary protein sequences were determined. Other proteins, such as the insulin-like growth factors (IGFs), the fibroblast growth factors (FGFs), epidermal growth factor (EGF), and S100β, were originally discovered based on nonneurotrophic activities and they were later found to act as neurotrophic agents on certain types of nerve cells. All of these factors were initially discovered, isolated, and purified based on their respective bioactivities and then their primary structures.