Many of the signaling pathways that regulate tissue specification and coordinate cellular differentiation during embryogenesis have been identified over the last decade. These pathways are integrated at the transcriptional level, enabling activation of specific developmental programs in a temporally and spatially restricted fashion. Such developmental events are usually thought of in terms of hierarchical relationships, in which the expression of upstream factors leads to the sequential activation of a linear cascade of downstream genes. Whereas these models provide a simplistic approach to understand complex cellular events, genetic and biochemical studies in mice and other model organisms provide ample evidence that many of these factors interact at multiple levels in vivo and emphasize the importance of considering these linear events in context. The purpose of this review is to emphasize the complexity of these regulatory networks during the early phases of mammalian kidney development, outlining some of the limitations and alternative approaches that are being used to explore the complex nature of these networks in vivo. Before describing these networks in detail, we will provide a brief overview of the main structural changes and tissue interactions involved in mammalian kidney development, and go on to describe some of the limitations of our current approaches to evaluate the role of these developmental pathways in vivo.