Use of reclaimed wastewater for agricultural irrigation is seen as an attractive option to meet agricultural water demands of a growing number of countries suffering from water scarcity. However, reclaimed wastewater contains pollutants which are introduced to the agro-environment during the irrigation process. While water reuse guidelines do consider selected classes of pollutants, they do not account for the presence of pollutants of emerging concern such as pharmaceuticals and the potential risks these may pose. Here we use source–pathway–receptor analysis (S–P–R) to develop a holistic framework for evaluating the impacts of pharmaceuticals, present in wastewater used for agricultural irrigation, on human and ecosystem health and evaluate the data availability for the framework components. The developed framework comprised of 34 processes and compartments but a good level of knowledge was available for only five of these suggesting that currently it is not possible to fully establish the impacts of pharmaceuticals in wastewater irrigation systems. To address this, work is urgently needed to understand the fate and transport of pharmaceuticals in arable soil systems and the effects of chronic low-level exposure to these substances on microbes, invertebrates, plants, wildlife and humans. In addition, research pertaining to the fate, uptake and effects of pharmaceutical mixtures and metabolites is lacking as well as data on bio-accessibility of pharmaceuticals after ingestion. Scientific advancements in the five areas prioritised in terms of future research are needed before we are able to fully quantify the agricultural and human health risks associated with reclaimed wastewater use.