Members of the Iroquois (Irx) homeodomain transcription factor gene family have been implicated in a variety of early developmental processes, including neural pre-patterning, tissue differentiation, neural crest development and cranial placode formation. Here, we report that, in zebrafish, the irx4a gene participates in specification of a number of placode derivatives that arise from the posterior placodal field. Specifically, differentiation of the trigeminal, epibranchial and lateral line placodes are affected when irx4a function is interrupted using antisense morpholino oligonucleotides. We show that both in the trigeminal ganglion and in the lateral line, irx4a is involved in controlling the number of sensory cells that develop. Other phenotypes observed in morphant embryos include misspecification of the heart chambers and failure of retinal ganglion and photoreceptor cell differentiation, functions described previously for Irx4 in other species. We also provide evidence that irx4a regulates the expression of the sox2 gene, both in the neural plate and in progenitor cells of the lateral line system. Our results point to irx4a as a critical gene for numerous developmental processes and highlight its role in the formation of placodal derivatives in vertebrates.