The therapy of parasitic diseases has relied, until recently, on the use of a very limited number of drugs, most of them of low efficacy, leading to side effects and in certain cases with high toxicity. This review focuses on the chemotherapy to treat diseases caused by Trypanosoma cruzi (Chagas disease), Trypanosoma b. gambiense and Trypanosoma b. rhodesiense (sleeping sickness), Plasmodium (malaria) and Leishmania (leishmaniasis). Therefore, we will summarize drugs currently available and future specific chemotherapy against these neglected diseases under clinical evaluation. The most advanced antichagasic candidates are represented by posaconazole, TAK-187 and albaconazole, which have completed their pre-clinical development as anti-T. cruzi agents, while new quinines concerning to ferroquine, tafenoquine and AQ-13 are in phase I or II of clinical trials as promising candidates for the treatment of malaria. Although parafuramidine has been under phase III clinical trials to treat Human African Trypanosomiasis (HAT), its development was discontinued due to liver problems. Finally, new approaches for the treatment of leishmaniasis were achieved by using miltefosine and, more recently, the aminoglycoside paromomycin, which was approved after clinical trials and, owing to its milder adverse effects and low cost, is being considered as a potential first-choice treatment for the disease. Thus, this review aims to highlight the available drugs to treat four endemic parasitic diseases, as well as promising therapeutic approaches and their corresponding targets under development, but it is not intended to be an exhaustive survey on the subject.