Although liver transplantation is the only therapy to halt the clinical manifestations of transthyretin (TTR) related familial amyloidotic polyneuropathy (FAP), the therapy has given rise to several problems. An alternative treatment is needed. After the precursor protein of amyloid fibrils in FAP was established in 1983, several different approaches have been investigated as an essential therapy for FAP: (1) reduction of variant TTR levels in plasma, (2) down regulation of variant TTR gene mRNA, (3) inhibition of amyloid deposition, (4) stabilization of the tetrameric TTR structure and (5) replacement of the variant TTR gene with the normal TTR gene (which can be achieved by liver transplantation or by gene therapy). In this chapter, we introduce these research strategies and trials and discuss the possibility of the optimal treatment for FAP.