Reverse osmosis (RO) has been employed as a key separation process in many industrial applications. In recent years, the use of positron annihilation spectroscopy (PAS) including positron annihilation lifetime spectroscopy (PALS) and Doppler broadening of annihilation radiation to characterise the internal structure of the skin layer of thin film composite membranes has renewed research interest for further development and optimisation of the RO process. In this paper, we highlight the need for better understanding of the skin layer internal structure. We review relevant PAS techniques that could provide an unprecedented level of insight to our understanding of the internal structure of the active skin layer of RO membranes. PALS data reported in previous studies revealed that commercially available RO membranes have a mean free-volume hole-radius of 0.20–0.29 nm in the active skin layer. Data corroborated from the literature show a good correlation between the mean free-volume hole-radius of RO membranes and the rejection of boric acid which can be considered as a model small and neutral solute. The data also highlight the need for a comprehensive inter-laboratory study to standardise free-volume hole-radius measurement using PALS. In addition to free-volume hole-radius, free-volume fraction and thickness of the active skin layer appear to be important membrane properties governing neutral solute rejection. A roadmap is suggested to enhance the understanding of the transport of small and neutral solutes in RO. This includes integrating PAS with other techniques (e.g. molecular dynamics simulation) to describe the internal structure of RO membranes.