In this work, we report a detailed discussion on the techniques and the requirements needed to enable Random Telegraph Noise (RTN) analysis as a tool to investigate device reliability. Starting with the understanding of the RTN signal properties, a set of best practices to perform measurements and data analysis is established to guarantee reliable results and a correct ensuing physical interpretation. It will be shown that combining dedicated and careful experiments with refined data analysis and comprehensive physics simulations is hence required to enable RTN analysis as a safe and innovative investigation tool for electron devices. The effectiveness of RTN analysis as an investigation tool is demonstrated on both FinFET and resistive memory devices: the parameters of RTN as observed in the experiments performed on FinFETs allow understanding the details of the defects generation during stress in such devices; RTN analysis on RRAM allows understanding the physical origin of RTN in these devices and to estimate the physical properties of defects involved in the phenomenon.