Crops irrigated with reclaimed wastewater or grown in biosolids-amended soils may take up pharmaceuticals and personal care product ingredients (PPCPs) through their roots. The uptake pathways followed by PPCPs and the propensity for these compounds to bioaccumulate in food crops are still not well understood. In this critical review, we discuss processes expected to influence root uptake of PPCPs, evaluate current literature on uptake of PPCPs, assess models for predicting plant uptake of these compounds, and provide recommendations for future research, highlighting processes warranting study that hold promise for improving mechanistic understanding of plant uptake of PPCPs. We find that many processes that are expected to influence PPCP uptake and accumulation have received little study, particularly rhizosphere interactions, in planta transformations, and physicochemical properties beyond lipophilicity (as measured by Kow). Data gaps and discrepancies in methodology and reporting have so far hindered development of models that accurately predict plant uptake of PPCPs. Topics warranting investigation in future research include the influence of rhizosphere processes on uptake, determining mechanisms of uptake and accumulation, in planta transformations, the effects of PPCPs on plants, and the development of predictive models.