Cocktails of pharmaceuticals are released in the environment after human consumption and due to the incomplete removal at the wastewater treatment plants. Pharmaceuticals are considered as contaminants of emerging concern and, a plethora of journal articles addressing their possible adverse effects have been published during the past 20 years. The emphasis during the early years of research within this field, was on the assessment of acute effects of pharmaceuticals applied singly, leading to results regarding their environmental risk, potentially not realistic or relevant to the actual environmental conditions. Only recently has the focus been shifted to chronic exposure and to the assessment of cocktail effects. To this end, this review provides an up-to-date compilation of 57 environmental and human toxicology studies published during 2000–2014 dealing with the adverse effects of pharmaceutical mixtures. The main challenges regarding the design of experiments and the analysis of the results regarding the effects of pharmaceutical mixtures to different biological systems are presented and discussed herein. The gaps of knowledge are critically reviewed highlighting specific future research needs and perspectives