This study evaluated the efficacy of albendazole, ivermectin, levamisole, mebendazole and praziquantel on monogeneans of Colossoma macropomum, based on in vitro and in vivo assays. In vitro assays indicated that albendazole (500, 100, 1,500 and 2,000 mg/L), ivermectin (200, 250, 300 and 350 mg/L) and levamisole (50, 75, 100 and 125 mg/L) were 100% effective against Anacanthorus spatulatus, Notozothecium janauachensis, Mymarothecium boegeri and Linguadactyloides brinkmanni, while mebendazole (125, 150, 175 and 200 mg/L) and praziquantel (5, 10, 15 and 20 mg/L) were ineffective. Fish mortality in 24 hr therapeutic baths with 500 mg/L of albendazole was 6.6%, but the behaviour of the animals remained unchanged, while 200 mg/L of ivermectin caused lethargy, signs of hypoxia and 100% mortality within 2 hr, and 125 mg/L of levamisole caused no mortality. The efficacy of 500 mg/L of albendazole was 48.6% in the 24 hr baths, while that of 125 mg/L levamisole was 88.2%. Although ivermectin showed in vitro efficacy, the lowest concentration used in baths was highly toxic to fish. Therefore, we recommend the use of 125 mg/L of levamisole to control and treat monogenean infestations on C. macropomum in fish farming.