Pharmaceuticals are biologically active, ubiquitous, low-level contaminants that are continuously introduced into the environment from both human and veterinary applications at volumes comparable to total pesticide loadings. Recent analytical advances have made possible the detection of a number of these compounds in environmental samples, raising concerns over potential nontarget effects to aquatic organisms, especially given the highly specific biologically active nature of these compounds. These concerns become paramount when the evolutionary conservation of metabolic pathways and receptors is taken into consideration, particularly in the case of aquatic plants, where a great deal of homology is displayed between the chloroplast and bacteria, as well as between other metabolic pathways across multiple phyla of biological organization. Common receptors have been identified in plants for a number of antibiotics affecting chloroplast replication (fluoroquinolones) transcription and translation (tetracyclines macrolides, lincosamides, P-aminoglycosides, and pleuromutilins), metabolic pathways such as folate biosynthesis (sulfonamides) and fatty acid biosynthesis (triclosan), as well as other classes of pharmaceuticals that affect sterol biosynthesis (statin-type blood lipid regulators). Toxicological investigations into the potency of these compounds indicates susceptibility across multiple plant species, although sensitivity to these compounds varies widely between blue-green algae, green algae, and higher plants in a rather inconsistent manner, except that Cyanobacteria are largely the most sensitive to antibiotic compounds. This differential sensitivity is likely dependent on differences in metabolic potential as well as uptake kinetics, which has been demonstrated for a number of compounds from another class of biologically active compounds, pesticides. The demonstration of conserved receptors and pathways in plants is not surprising, although it has been largely overlooked in the risk assessment process to date, which typically relies heavily on physiological and/or morphological endpoints for deriving toxicity data. However, a small number of studies have indicated that measuring the response of a pathway- or receptor-specific target in conjunction with a physiological endpoint with direct relatedness can yield sublethal responses that are two to three times more sensitive that the traditional gross morphological endpoints typically employed in risk assessment. The risk assessment for this review was based almost entirely on evaluations of gross morphological endpoints, which generally indicated that the risk pharmaceuticals pose to aquatic plants is generally low, with a few exceptions, particularly blue-green algae exposed to antibiotics, and both green and blue-green algae exposed to triclosan. It is critical to note, however, that the application of sublethal pathway or receptor-specific responses in risk assessment has largely been unconsidered, and future research is needed to elucidate whether evaluating the toxicity of pharmaceuticals using these endpoints provides a more sensitive, subtle, yet meaningful indication of toxicity than the traditional endpoints used in prospective and retrospective risk assessments for aquatic plants.