Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) represent one of the main therapeutic classes of molecules contaminating aquatic ecosystems worldwide. NSAIDs are commonly and extensively used for their analgesic, antipyretic and anti-inflammatory properties to cure pain and inflammation in human and veterinary therapy. After use, NSAIDs are excreted in their native form or as metabolites, entering the aquatic ecosystems. A number of monitoring surveys has detected the presence of different NSAIDs in freshwater ecosystems in the ng/L – μg/L concentration range. Although the concentrations of NSAIDs in surface waters are low, the high biological activity of these molecules may confer them a potential toxicity towards non-target aquatic organisms. The present review aims at summarizing toxicity, in terms of both acute and chronic toxicity, induced by the main NSAIDs detected in surface waters worldwide, namely acetylsalicylic acid (ASA), paracetamol (PCM), diclofenac (DCF), ibuprofen (IBU) and naproxen (NPX), both singularly and in mixture, towards freshwater invertebrates. Invertebrates play a crucial role in ecosystem functioning so that NSAIDs-induced effects may result in hazardous consequences to the whole freshwater trophic chain. Acute toxicity of NSAIDs occurs only at high, unrealistic concentrations, while sub-lethal effects arise also at low, environmentally relevant concentrations of all these drugs. Thus, further studies represent a priority in order to improve the knowledge on NSAID toxicity and mechanism(s) of action in freshwater organisms and to shed light on their real ecological hazard towards freshwater communities.