Pharmaceutically active compounds (PhACs) have recently received wide attention in the scientific community due to their extensive consumption for human health and consequent discharge to the environment. Release of PhACs into the environment, even in trace amounts, can cause serious environmental damage. This has become a major concern and their removal from water sources is a priority. Although a few PhACs are efficiently removed in wastewater treatment plants (WWTPs), others remain recalcitrant, and their release is causing damage. In this review, the current state of the art on the biological removal processes of sulfonamide sulfamethoxazole (SMX), the anticonvulsant carbamazepine (CBZ), and steroid estrogens 17b-estradiol (E2) and 17a-ethinylestradiol (EE2) are discussed, along with their environmental impact. Other systems beyond activated sludge, such as membrane bioreactors, enzymatic membrane reactors, fungi treatments and hybrid systems are also becoming of major interest and are being evaluated for the removal of these compounds. Future perspectives are addressed.