The zebrafish (Danio rerio) is a model organism making useful contributions in many areas of biological research. Zebrafish have proven particularly suitable for studying early development. The transparency and ex vivo development of zebrafish embryos means that early embryology can be easily visualized, especially using transgenic strains expressing fluorophores marking tissues of interest. High fecundity and tolerance of dense mutagenesis have made it a practical model for forward genetic screening and creation of mutagenized libraries from which stable mutant alleles can be recovered. Transient genetic manipulation by microinjection of mRNA (overexpression) or antisense morpholino oligonucleotides (knockdown) provide convenient methods for functionally assessing genetic regulatory pathways without the need for extended breeding strategies. A standout example of the utility of this model has been its application to modeling of the earliest stages of hematopoiesis. Zebrafish developmental hematopoiesis shows close correspondence to the development of the mammalian hematopoietic system and is regulated by conserved molecular pathways. This review highlights key recent studies that have used this model to provide insights into vertebrate hematopoietic development and innate immunity.