A total of 56 species of West Indian Poecilosclerida incorporated in the collections of the Zoological Museum of Amsterdam is described and fully illustrated. Poecilosclerid type specimens of the Duchassaing & Michelotti (1864) collection housed in Amsterdam are redescribed. Next to these 29 new species are erected: Mycale arndti, M. diversisigmata, M. americana, M. magnirhaphidifera, Strongylacidon poriticola, S. viridis, S. rubra. Batzella rosea, Hemitedania baki, Lissodendoryx strongylata, Forcepia grandisigmata, Coelosphaera hechteli, Crella chelifera, Hymedesmia jamaicensis, H. palmatichelifera, H. agariciicola, H. curacaoensis, Acanthancora coralliophila, Clathria simpsoni, C. bulbotoxa, C. hymedesmioides, Rhaphidophlus minutus, R. raraechelae, R. isodictyoides, R. oxeotus, Artemisina melana, Plocamilla barbadensis, Desmacella polysigmata, and Didiscus flavus. The following new combinations and synonymy designations are introduced: Mycale angulosa (Duch. & Mich., 1864) for Zygomycale parishi of authors, Acarnus souriei (Lévi, 1952) for Acanthacarnus souriei, Forcepia trilabis Boury-Esnault (1973) for Ectoforcepia trilabis, Phorbas amaranthus Duch. & Mich., 1864, for Merriamium tortuganensis De Laubenfels, 1936, Clathria affinis (Topsent, 1889) for Hymeraphia affinis, and Clathria ferrea (De Laubenfels, 1936) for Fisherispongia ferrea. Several new combinations are suggested for species not represented in the present collection, but studied for comparative reasons. The genera and families of West Indian Poecilosclerida are discussed, and remarks are made on their distribution and ecology. Data on reproductive activity noted in the studied specimens are given in separate table.