The olfactory system is a good model to study the mechanisms underlying guidance of growing axons to their appropriate targets. The formation of the olfactory bulb involves differentiation of several populations of cells and the initiation of the central projections, all under the temporal and spatial patterns of gene expression. Moreover, the nature of interactions between the olfactory epithelium, olfactory bulb and olfactory cortex at early developmental stages is currently of great interest. To explore these questions more fully, the present review aims to correlate recent data from different developmental studies, to gain insight into the mechanisms involved in the specification and development of the olfactory system. From our studies in the pax6 mutant mice (Sey(Neu)/Sey(Neu)), it was concluded that the initial establishment of the olfactory bulb central projections is able to proceed independently of the olfactory sensory axons from the olfactory epithelium. The challenge that now remains is to consider the validity of the olfactory bulb as an independent development domain. In the course of evaluating these ideas, we will review the orchestra of molecular cues involved in the formation of the projection from the OB to the olfactory cortex.