For more than two decades, chloroquine (CQ) was largely and deliberate used as first choice drug for malaria treatment. However, worldwide increasing cases of resistant strains of Plasmodium have hampered its use. Nevertheless, CQ has recently been tested as adjunct therapy in several inflammatory situations, such as rheumatoid arthritis and transplantation procedures, presenting intriguing and promising results. In this review, we discuss recent findings and CQ mechanisms of action vis-à-vis its use as a broad adjunct therapy.