Reliable and adequate removal of small and uncharged trace organic chemicals, particularly N-nitrosodimethylamine (NDMA) that is carcinogenic and known to occur in treated effluent, is essential for implementing direct potable water use. This study provides new insights to explain the low rejection of NDMA and other N-nitrosamines by reverse osmosis (RO) membranes by examining the role of molecular size and polarity in their molecular structure. The results show that molecular weight is not a suitable molecular property for evaluating the rejection of small uncharged chemicals. In this study, NDMA and two other uncharged chemicals have similar molecular weights (i.e., 72−74 g/mol), but their rejection by the ESPA2 RO membrane varied considerably from 30 to 88%. Instead, a minimum projection area was identified as a more suitable molecular property, indicating that size exclusion plays a primary role in their rejection. It was also determined that chemicals with more nitrogen atoms in their chemical structure consistently showed rejections lower than those of their similarly sized counterparts. The results suggest that chemicals bearing more nitrogen atoms (e.g., NDMA) have higher affinity to amide or amine functional group of a polyamide RO membrane possibly through hydrogen bonding interactions.