What is the Achilles’ heel of academic Fault Detection and Isolation (FDI) methods when it comes to application to real aircraft systems? This paper discusses some major and decisive issues that stand in the way of their transition from lab developments and simulations to real life applications in aeronautics. Often underestimated by academics, these issues determine the survivability of a new design for final V&V (Verification & Validation) activities. The paper recalls some practical items that should be considered at the design stage to help reach high Technological Readiness Level (TRL) scales for a given FDI algorithm. The paper will also take a look in the future and the way forward to anticipate future needs.